Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_998_Библиотеки_им_академика_М_И_Перельмана
.pdf
176
https://t.me/medicina_free
J. Zeller and S. U. Eisenhardt
oxygen species (ROS) and the activation of the
complement system [56–59].
In plastic surgery, reperfusion injury occurs
primarily in the course of microsurgical free tissue transfer for reconstruction after tumor or
injury, and after replantation of traumatic amputated limbs or their parts [53]. In a recent
benchmark- study, we demonstrated that IRI in
free human muscle tissue transplants launches
molecular changes that lead to a signicant upregulation of inammatory parameters, transmigration of inammatory cells, and angiogenesis
[60]. In these pathological inammatory conditions, CRP plays a causal role that leads to aggravation of inammation and tissue injury [61]. We
lately conrmed the signicance of bioactive
CRP deposits localized to myocardial tissue in a
rat disease model of ischemia/reperfusion injury.
The deposition of a tissue-bound conformer of
CRP collocated with leukocytes was identied
perivascular exclusively in the infarcted regions,
but not in non-infarcted segments. Additional
data demonstrated an agent-dependent stabilization of the circulating CRP and the prevention of
an alteration to a conformer of CRP that exhibits
strong pro-inammatory properties. The blocking of the dissociation resulted in a distinct
decrease of CRP deposition in ischemic perturbed muscle tissue and an inhibition of the
CRP-mediated increase of leukocytic activity.
This emphasizes the pivotal role of CRP alteration in the inammatory exacerbation and concurrently the feasibility of this therapeutic
approach [61]. Therefore, prolonged ischemia
time during free ap reconstruction surgery may
end in ap failure due to aggravating effects of
the CRP deposits.
(DAMP) and cause a rapid increase of acute
phase reactants [63]. Serum levels of both the
acute phase reactant CRP and complement have
been shown to be elevated proportionally to the
area and the depth of the skin involved in burn
wounds [64–68]. If infection occurred in the
burned area, the resulting acute phase response,
and therefore the CRP production, was increased
and prolonged [69]. Interestingly, however, a
recent study conducted in our laboratories demonstrated that the deposition of C-reactive protein
was restricted to burned areas, while healthy skin
stayed unaffected. We found the deposited CRP
co-localized with white blood cells and suggest a
pivotal role of CRP in severe burns [62].
Regarding the clinical outcome, elevated levels
of systemic complement have been linked to the
progression of severe burn injuries and higher
mortality [70, 71]. Furthermore, commonly
encountered sequelae of major burn wounds as
the intravascular hemolysis and thrombosis and
deforming and disabling scar formation were
reported to be related with increased complement
levels [72–74]. Both the concordant rise of CRP
and complement serum levels and the CRPmediated and complement-driven inammation
are hinting at a signicant causal role of CRP in
the progression of pathogenesis in thermal
injured patients. Thus, therapies that intend to
lower CRP serum levels appear expedient to
reduce the inammatory response and improve
prognosis [75].
17.3 Ischemia/Reperfusion Injury
(IRI) andAllogeneic
Transplantation
17.2.2 CRP inSevere Burns
Another clinical relevant occurrence of CRP in
plastic surgery is in burn wounds/thermal injuries. In this form of critical tissue damage, numerous cells simultaneously undergo critical damage
leading to apoptosis and necrosis [62]. Thereby
exposed debris and apoptotic bodies function as
danger-associated molecular pattern molecules
The transplantation of a functional composition
of multiple tissues such as bone, muscle, nerves,
and skin, summarized in the term Vascularized
Composite Allotransplant (VCA), provides
potential treatment solutions for complex tissue
defects. The technology and knowledge for this
upcoming branch of transplant surgery derive
from clinical experience and research efforts in
solid organ transplantations (e.g., heart and kidney), and became clinical reality with the rst
17 Targeting C-Reactive Protein inInammatory Disease
https://t.me/medicina_free
177
successful human allogeneic hand transplantation in 1998 [76]. Unlike autologous transplantations, composite tissue grafts of allogeneic origin
are subject to immune rejection by the recipient.
Thus, clinicians face similar issues encountered
in solid organ transplantation with the exception
that VCA is usually not considered a life-saving
treatment. The role of the innate immune system
in recognition and eradication of microbial
pathogens is relatively well understood [77, 78].
However, it remains elusive how sterile allografts
trigger the maturation of antigen presenting cells
(APC) in the absence of microbial-derived signals [79]. The so-called “danger hypothesis”, a
commonly accepted paradigm on the origin of
APC maturation, holds particles of apoptotic and
necrotic cells (damage-/danger-associated
molecular patterns, DAMPs) in the transplanted
tissue responsible for the activation of the innate
immune response [80, 81]. Recently, it has been
shown that innate recognition of allogeneic nonself by monocytes can initiate graft rejection in
allogeneic transplantation that might represent
another potential therapeutic target [79].
Furthermore, large retrospective studies on allogeneic organ transplantation demonstrated that
an episode of acute graft rejection is a major risk
factor for chronic rejection and a signicant predictor of long-term allograft survival [82].
Consequently, solid organ transplantation and
VCA are considered to be distinctively vulnerable to ischemia/reperfusion injury (IRI).
Reecting its novelty and therapeutic potential,
the pathogenesis of vascularized composite allotransplants failure and the role of IRI- and CRPinduced activation of innate immunity are most
in need of further investigation.
a central pore forming a cyclic multimeric discoid wrath [84]. Each monomer of the pentameric protein is of identical molecular weight and
structure [85]. Two antiparallel β-sheets of 206
amino acids in total length form one globular
monomer of approximately 23 kDa molecular
mass with a attened Swiss roll typology [86,
87]. Electron microscopic and crystallographic
data indicate that all CRP subunits show a specic orientation in the pentameric conformation.
Therefore, the resulting two sides of the disc
were suggested to have distinctive functions.
1. On one face, the so-called B face (or binding
face), a hydrophobic pocket is presumably
formed for the ligand-recognition of phosphocholine (PC) exposed on damaged or apoptotic cell membranes and pathogens. Two
coordinated Ca
2+
-ions adjected to the hydrophobic pocket mediate the major interaction
between CRP and the phosphate head group
of PC (Fig.17.2) [84].
2. The opposite side is dominated by a single
long α-helix and a deep and narrow cleft formation. Residues located or associated with
this cleft enable the interaction with complement factor C1q and various Fcγ receptors,
therefore, this face functions as the effector
face (also “A” face) (Fig.17.2).
The inaccessible location of these residues in
the circulating pentameric conguration, however, suggests that the circulating pentamer is not
the interacting form for host defense functions
[32, 34, 84, 86, 88–91] and the pCRP is more a
precursor form that does not signicantly interact
with the complement system [92].
17.4 From Structure toFunction
The pentraxin protein family is characterized by
a cyclic pentameric assembly, sequence homology, and a calcium-dependent interaction with its
ligands, respectively [83]. The interactions
between the subunits in the CRP pentamer
involve numerous electrostatic and hydrophobic
bonding that arrange them symmetrically around
17.5 Conformational Changes
Alter theFunction ofCRP
A dissociation mechanism on activated platelets
that causes a conformational change from the circulating native pentamer (pCRP) to the monomeric subunits of CRP (mCRP) has been
identied [93]. Local environmental changes in
pH (4.5–5.5) [94] and the accumulation of
178
1,6-bis(phosphocholine)-hexane
https://t.me/medicina_free
J. Zeller and S. U. Eisenhardt
a
binding face effector face
c
b
effector face
binding face
Fig. 17.2 Model of pCRP and its interaction with 1,6-bis(phosphocholine)-hexane
oxygen radicals [95] during inammation, as in
atherosclerosis, appear to facilitate the dissociation of pCRP in the site of inammation. We
demonstrated the process of pCRP dissociating
to mCRP after binding to activated endothelial
cell membranes in areas of acute inammation in
an invivo rat model [61]. The emerging knowledge indicates that CRP can occur invivo in at
least two distinct conformers with distinct bioactivities, respectively. The pro-inammatory
capacity formerly attributed to CRP most likely
is because of mCRP deposits. Under this new
proposal, mCRP exhibits a signicantly stronger
binding potential to complement C1q compared
with pCRP [96]. Accompanied with the alteration in structure, the functional properties of CRP
in cell-interaction vary. Along with the dissociation to mCRP, CRPs obtain increased ability to
activate monocytes. Activated monocytes show
adhesion and transmigration, further, increased
ROS activity, overall factors contributing in
aggravating tissue inammation [93]. In line with
binding face
effector face
CD68 (anti-macrophages)9C9 (anti-mCRP)8D8 (anti-pCRP)
pre- ischemiapost- reperfusion
17 Targeting C-Reactive Protein inInammatory Disease
https://t.me/medicina_free
179
Fig. 17.3 Detection of mCRP and CD68+ cells in postischemic human striated muscle tissue.
Immunohistochemical staining of muscle tissue with conformation specic antibodies. Antibody clone 8D8 was
used to detect pCRP, and clone 9C9 was used for the
detection of the monomeric conformation of CRP
(mCRP). Right panel shows the co-localization of CD-68
that, we detected in both human striated muscle
biopsies of ischemia/reperfusion injury and
biopsies of infarcted myocardium, mCRP, but not
pCRP in the ischemia-affected tissue, which colocalizes with CD-68 positive monocytes/macrophages (Figs. 17.3 and 17.4) [61]. Recently,
Braig et al. [97] identied a novel proinammatory mechanism of CRP (Fig. 17.1).
The ndings suggest a cascade in which circulating pCRP undergoes a structural change by binding to cell-derived microvesicles without
disrupting the pentameric symmetry (pCRP∗). In
this invivo and invitro-observed process, circulating pCRP binds to perturbed plasma membrane of activated monocytes and is subsequently
positive monocytes/macrophages in the injured tissue.
Reprinted with permission from “The Dissociation of
Pentameric to Monomeric C-Reactive Protein Localizes
and Aggravates Inammation: In vivo Proof of a Powerful
Pro-Inammatory Mechanism and a New AntiInammatory Strategy” by Thiele etal., Circulation, 2014
[61]
released on microvesicles. Microvesicles bud
from cell membrane as lysophosphatidylcholineenriched spheres of 100–1000 nm in diameter
[98]. The microvesicle-bound pCRP undergoes
structural changes and produce pCRP∗, a CRP
isoform expressing the neoepitope of mCRP
while maintaining an overall pentameric conguration. Thus, a CRP isoform, which, in contrast to
circulating pCRP, exhibits a pro-inammatory
prole, is released into the surrounding tissue
bound to plasma membrane-derived microvesicles [97]. In accordance with these ndings, a
prior study reported expression of neoepitopes on
circulating microvesicles in patients following
myocardial infarction [99].
180
Non-infarcted myocardiumInfarcted myocardium
9C9 (anti-mCRP)
8D8 (anti-pCRP)
negative control
https://t.me/medicina_free
J. Zeller and S. U. Eisenhardt
Fig. 17.4 Accumulation of mCRP in infarcted myocardium. Immunohistochemical staining of human postmortem samples following myocardial infarction. The
used conformational specic antibodies show signicant
deposition of monomeric CRP in the infarcted tissue, but
only slightly (small amounts of peri-vascular staining) in
the non-infarcted tissue. In both the pCRP staining and the
sociating process of the inert circulating pentameric CRP to the distinctively pro-inammatory
monomeric derivative allows for a new view on
CRP in inammatory reactions. In addition, the
This novel understanding of the localized dis-
control, there is no signicant staining detectable.
Reprinted with permission from “The Dissociation of
Pentameric to Monomeric C-Reactive Protein Localizes
and Aggravates Inammation: In vivo Proof of a Powerful
Pro-Inammatory Mechanism and a New AntiInammatory Strategy” by Thiele etal., Circulation, 2014
[61]
ndings emphasize the molecular structurefunction relationships, and therefore highlight the
dissociation process and mCRP as a potential
therapeutic target of practical, as well as theoretical importance.
17 Targeting C-Reactive Protein inInammatory Disease
https://t.me/medicina_free
181
17.6 Therapeutic Targeting
ofC-Reactive Protein
Calor, dolor, tumor, rubor –a nearly 2000years
old attempt to characterize inammation in four
cardinal signs. Two millennia after Aulus
Cornelius Celsus rst recorded these words in his
work De Medicina (De Medicina, AD25), our
accumulated knowledge for the complexity of
the processes in inammation make such a simplication unreasonable and still much remains
elusive. Yet, we know inammation is a physiological and inevitable response to tissue injury
and contributes to life preservation of the host, as
reected by the increased risk of severe infections
in patients with deciencies in principal components of the inammatory process [100–102].
Therefore, anti-inammatory strategies represent
a two-edged sword and a sufcient inhibition
must be ultimately purchased by a variety of considerable side effects. Currently, available antiinammatory drugs, e.g., non- steroidal
anti-inammatory drugs (NSAID), cytokineinhibiting biologicals, or glucocorticoids exhibit
systemic adverse effects even after local administration [103, 104], impair benecial processes of
inammation as wound repair and angiogenesis
[105–107], and increase vulnerability for infections and pathogens [108–112].
17.7 Why Is CRP aRewarding
Target?
Based on x-ray crystallography data [84], Pepys
etal. [113] designed a proof-of-concept compound,
1,6-bis (phosphocholine)-hexane (1,6- bisPC), that
inhibits the CRP-induced actions. The reported
agent represents a specic small- molecule inhibitor of CRP. The concept utilizes the phosphocholine (PC) binding-site on the recognition face of
CRP.It is suggested that the palindromic phosphocholine dimer crosslinks two pentameric CRP molecules, and thus make the ligand binding-site
inaccessible for PC, thereby impairing pCRP activity (Fig.17.2) [113]. In a recent study, we approved
the presumed anti- inammatory potential of 1,6bisPC.The agent reduced the localized inammatory response in a myocardial ischemia/reperfusion
model by stabilization of pCRP and prevention of
CRP dissociation. The localized deposition of
mCRP to the site of primary tissue impairment was
markedly reduced. 1,6-bisPC effectively inhibited
generation of mCRP, and consequently its proinammatory potential to exacerbate the local
inammation was abrogated [61]. Additionally, we
demonstrated that 1,6-bisPC exhibits the capability
to attenuate the CRP-driven exacerbation of inammation by inhibiting the interaction between pCRP
and cell-derived microvesicles. We were able to
substantiate our hypothesis by intravital microscopic tracking of pCRP in inamed muscle tissue.
Preincubation of pCRP with the small-molecule
inhibitor 1,6-bisPC resulted in an incapacity of
pCRP to bind phosphocholine, thus no pCRP was
detectable on transmigrated leukocytes [
characteristics of the CRP dissociation as a local
process and the following mCRP-driven exacerbation of inammation emphasize their attractiveness
as a rewarding therapeutic target (Fig.17.5). After
the application of 1,6-bisPC in animal models no
signicant adverse effects were notable, and 1,6bisPC alone showed neither pro- nor anti-inammatory properties [61, 113]. It is fair to assume
that an anti-inammatory therapy based on 1,6bisPC has no major systemic side effects. It is
more likely that anti-CRP therapy inhibits the
exacerbation of pre-existing tissue- damage than
the favorable inammation in wound healing signicantly [114, 115]. In the light of the reality that
although CRP has been conserved throughout the
evolution without any mutation, the potentially
harmful effects of a therapeutic CRP inhibition
cannot be excluded by now.
However, two already known shortcoming/
deciencies of this compound should be
addressed beforehand.
1. 1,6-bis(phosphocholine)-hexane exhibits a rel-
atively low afnity for pCRP.Therefore, higher
quantities of the substance must be applied
invivo to achieve a sufcient effect (113).
2. 1,6-bis(phosphocholine)-hexane has poor
pharmacokinetics. Due to its polarity, the
bioavailability of 1,6-bis(phosphocholine)-
hexane after oral administration remains
unsatisfactory, and it is rapidly cleared from
circulation [113].
97]. The
182
https://t.me/medicina_free
J. Zeller and S. U. Eisenhardt
Fig. 17.5 Model of the therapeutic targeting of CRP
using 1,6-bis(phosphocholine)-hexane (1,6-bis PC). 1,6bis PC (white-green pill) inhibits the interaction of circulating pentameric CRP with recruited leukocytes.
Subsequent release of membrane-derived pro-
17.8 Conclusions
Recent data identied and characterized the conformational change of CRP as the key event in a
novel pro-inammatory cascade. Proof-of- concept
studies conducted demonstrated the implications
and feasibility of therapeutic mCRP inhibition in
various circumstances. In ischemia/reperfusion
injury, mCRP exacerbates the local inammation
by activation of the classical complement pathway
and massive leukocyte recruitment. In acute transplant rejection, mCPR mediates the innate immune
response and considerably worsen the long-term
allograft survival. The innovative small-molecule
inhibitor 1,6-bis(phosphocholine)-hexane abrogates these pro-inammatory capacities of
mCRP. Yet, the therapeutic targeting of the CRP
dissociation seems to exclusively affect the aggravation of local inammatory processes, whilst
inammatory microvesicles and leukocyte-endothelium
interaction is inhibited. Therefore, 1,6-bisPC attenuates
the inammatory response to the ischemia/reperfusion
injury and prevents an exacerbation of the local
inammation
benecial responses of the immune system
proceed widely undisturbed. Our new understanding of the pathogenesis in CRP-driven exacerbation provides the impetus to change the concept of
post- surgical treatment in both autogeneic and
allogeneic transplantation.
References
1. Tillett WS, Francis T.Serological reactions in pneu-
monia with a non-protein somatic fraction of pneumococcus. J Exp Med. 1930;52(4):561–71.
2. Yeh ET, Palusinski RP.C-reactive protein: The pawn
has been promoted to queen. Curr Atheroscler Rep.
2003;5:101.
3. Thiele JR, Zeller J, Bannasch H, Stark GB, Peter
K, Eisenhardt SU. Targeting C-reactive protein in
inammatory disease by preventing conformational
changes. Mediat Inamm. 2015;2015:372432.
4. Zhang D, Sun M, Samols D, Kushner I. STAT3
participates in transcriptional activation of the
17 Targeting C-Reactive Protein inInammatory Disease
https://t.me/medicina_free
183
C-reactive protein gene by interleukin-6. J Biol
Chem. 1996;271(16):9503–9.
5. Ganter U, Arcone R, Toniatti C, Morrone G, Ciliberto
G.Dual control of C-reactive protein gene expression by interleukin-1 and interleukin-6. EMBO J.
1989;8(12):3773–9.
6. Woo P, Korenberg JR, Whitehead
AS. Characterization of genomic and complementary DNA sequence of human C-reactive protein,
and comparison with the complementary DNA
sequence of serum amyloid P component. J Biol
Chem. 1985;260(24):13384–8.
7. Macintyre S, Samols D, Dailey P. Two carboxylesterases bind C-reactive protein within the
endoplasmic reticulum and regulate its secretion
during the acute phase response. J Biol Chem.
1994;269(39):24496–503.
8. Macintyre SS, Kushner I, Samols D. Secretion of
C-reactive protein becomes more efcient during
the course of the acute phase response. J Biol Chem.
1985;260(7):4169–73.
9. Yue CC, Muller-Greven J, Dailey P, Lozanski
G, Anderson V, Macintyre S. Identication of a
C-reactive protein binding site in two hepatic carboxylesterases capable of retaining C-reactive protein within the endoplasmic reticulum. J Biol Chem.
1996;271(36):22245–50.
10. Volanakis JE. Human C-reactive protein: expression, structure, and function. Mol Immunol.
2001;38(2-3):189–97.
11. Moshage HJ, Roelofs HM, van Pelt JF, Hazenberg
BP, van Leeuwen MA, Limburg PC, Aarden LA,
Yap SH. The effect of interleukin-1, interleukin-6
and its interrelationship on the synthesis of serum
amyloid A and C-reactive protein in primary cultures
of adult human hepatocytes. Biochem Biophys Res
Commun. 1988;155(1):112–7.
12. Pfafin A, Schleicher E. Inammation markers in
point-of-care testing (POCT). Anal Bioanal Chem.
2009;393(5):1473–80.
13. Yasojima K, Schwab C, McGeer EG, McGeer
PL. Human neurons generate C-reactive protein
and amyloid P: upregulation in Alzheimer’s disease.
Brain Res. 2000;887(1):80–9.
14. Jabs WJ, Logering BA, Gerke P, Kreft B, Wolber
EM, Klinger MH, Fricke L, Steinhoff J.The kidney
as a second site of human C-reactive protein formation invivo. Eur J Immunol. 2003;33(1):152–61.
15. Ramage L, Proudfoot L, Guy K. Expression of
C-reactive protein in human lung epithelial cells
and upregulation by cytokines and carbon particles.
Inhal Toxicol. 2004;16(9):607–13.
16. Jialal I, Devaraj S, Venugopal SK. C-reactive protein: risk marker or mediator in atherothrombosis?
Hypertension. 2004;44(1):6–11.
17. Kuta AE, Baum LL. C-reactive protein is produced by a small number of normal human
peripheral blood lymphocytes. J Exp Med.
1986;164(1):321–6.
18. Calabro P, Willerson JT, Yeh ET. Inammatory
cytokines stimulated C-reactive protein production
by human coronary artery smooth muscle cells.
Circulation. 2003;108(16):1930–2.
19. Yasojima K, Schwab C, McGeer EG, McGeer
PL. Generation of C-reactive protein and complement components in atherosclerotic plaques. Am J
Pathol. 2001;158(3):1039–51.
20. Calabro P, Chang DW, Willerson JT, Yeh ET.Release
of C-reactive protein in response to inammatory cytokines by human adipocytes: linking obesity to vascular inammation. J Am Coll Cardiol.
2005;46(6):1112–3.
21. Hutchinson WL, Noble GE, Hawkins PN, Pepys
MB. The pentraxins, C-reactive protein and serum
amyloid P component, are cleared and catabolized by
hepatocytes invivo. J Clin Invest. 1994;94(4):1390–6.
22. Vigushin DM, Pepys MB, Hawkins PN.Metabolic
and scintigraphic studies of radioiodinated human
C-reactive protein in health and disease. J Clin
Invest. 1993;91(4):1351–7.
23. Haverkate F, Thompson SG, Pyke SD, Gallimore
JR, Pepys MB.Production of C-reactive protein and
risk of coronary events in stable and unstable angina.
European Concerted Action on Thrombosis and
Disabilities Angina Pectoris Study Group. Lancet.
1997;349(9050):462–6.
24. Koenig W, Sund M, Frohlich M, Fischer HG, Lowel
H, Doring A, Hutchinson WL, Pepys MB.C-Reactive
protein, a sensitive marker of inammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the
MONICA (Monitoring Trends and Determinants
in Cardiovascular Disease) Augsburg Cohort Study,
1984 to 1992. Circulation. 1999;99(2):237–42.
25. Rohde LE, Hennekens CH, Ridker PM. Survey
of C-reactive protein and cardiovascular risk factors in apparently healthy men. Am J Cardiol.
1999;84(9):1018–22.
26. Ridker PM, Hennekens CH, Buring JE, Rifai
N. C-reactive protein and other markers of
inammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342(12):836–43.
27. Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL,
Rebuzzi AG, Pepys MB, Maseri A. The prognostic value of C-reactive protein and serum amyloid
a protein in severe unstable angina. N Engl J Med.
1994;331(7):417–24.
28. Ridker PM, Glynn RJ, Hennekens CH.C-reactive
protein adds to the predictive value of total and HDL
cholesterol in determining risk of rst myocardial
infarction. Circulation. 1998;97(20):2007–11.
29. Ridker PM, Buring JE, Shih J, Matias M,
Hennekens CH. Prospective study of C-reactive
protein and the risk of future cardiovascular events
among apparently healthy women. Circulation.
1998;98(8):731–3.
30. Cermak J, Key NS, Bach RR, Balla J, Jacob HS,
Vercellotti GM. C-reactive protein induces human
peripheral blood monocytes to synthesize tissue factor. Blood. 1993;82(2):513–20.
31. Ramani M, Khechai F, Ollivier V, Ternisien C,
Bridey F, Hakim J, de Prost D. Interleukin-10 and
184
https://t.me/medicina_free
J. Zeller and S. U. Eisenhardt
pentoxifylline inhibit C-reactive protein-induced
tissue factor gene expression in peripheral human
blood monocytes. FEBS Lett. 1994;356(1):86–8.
32. Chang MK, Binder CJ, Torzewski M, Witztum
JL. C-reactive protein binds to both oxidized
LDL and apoptotic cells through recognition of
a common ligand: Phosphorylcholine of oxidized phospholipids. Proc Natl Acad Sci U S A.
2002;99(20):13043–8.
33. Volanakis JE, Wirtz KW. Interaction of C-reactive
protein with articial phosphatidylcholine bilayers.
Nature. 1979;281(5727):155–7.
34. Volanakis JE, Narkates AJ. Interaction of
C-reactive protein with articial phosphatidylcholine bilayers and complement. J Immunol.
1981;126(5):1820–5.
35. Kushner I, Kaplan MH. Studies of acute phase
protein. I. An immunohistochemical method for
the localization of Cx-reactive protein in rabbits.
Association with necrosis in local inammatory
lesions. J Exp Med. 1961;114:961–74.
36. Kushner I, Rakita L, Kaplan MH.Studies of acutephase protein. II.Localization of Cx-reactive protein
in heart in induced myocardial infarction in rabbits.
J Clin Invest. 1963;42:286–92.
37. Bharadwaj D, Stein MP, Volzer M, Mold C, Du
Clos TW.The major receptor for C-reactive protein
on leukocytes is fcgamma receptor II.J Exp Med.
1999;190(4):585–90.
38. Mold C, Gresham HD, Du Clos TW.Serum amyloid
P component and C-reactive protein mediate phagocytosis through murine Fc gamma Rs. J Immunol.
2001;166(2):1200–5.
39. Claus DR, Siegel J, Petras K, Osmand AP, Gewurz
H. Interactions of C-reactive protein with the rst
component of human complement. J Immunol.
1977;119(1):187–92.
40. Lagrand WK, Niessen HW, Wolbink GJ, Jaspars
LH, Visser CA, Verheugt FW, Meijer CJ, Hack
CE.C-reactive protein colocalizes with complement
in human hearts during acute myocardial infarction.
Circulation. 1997;95(1):97–103.
41. Mold C, Gewurz H, Du Clos TW. Regulation
of complement activation by C-reactive protein.
Immunopharmacology. 1999;42(1-3):23–30.
42. Kaplan MH, Volanakis JE.Interaction of C-reactive
protein complexes with the complement system.
I. Consumption of human complement associated
with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin. J Immunol.
1974;112(6):2135–47.
43. Kilpatrick JM, Volanakis JE.Opsonic properties of
C-reactive protein. Stimulation by phorbol myristate
acetate enables human neutrophils to phagocytize C-reactive protein-coated cells. J Immunol.
1985;134(5):3364–70.
44. Tebo JM, Mortensen RF. Characterization and
isolation of a C-reactive protein receptor from the
human monocytic cell line U-937. J Immunol.
1990;144(1):231–8.
45. Du Clos TW. C-reactive protein reacts with the
U1 small nuclear ribonucleoprotein. J Immunol.
1989;143(8):2553–9.
46. Pepys MB, Booth SE, Tennent GA, Butler PJ,
Williams DG. Binding of pentraxins to different
nuclear structures: C-reactive protein binds to small
nuclear ribonucleoprotein particles, serum amyloid
P component binds to chromatin and nucleoli. Clin
Exp Immunol. 1994;97(1):152–7.
47. Gershov D, Kim S, Brot N, Elkon KB.C-Reactive
protein binds to apoptotic cells, protects the cells
from assembly of the terminal complement components, and sustains an antiinammatory innate
immune response: implications for systemic autoimmunity. J Exp Med. 2000;192(9):1353–64.
48. Merrill JP, Murray JE, Harrison JH, Guild
WR.Successful homotransplantation of the human
kidney between identical twins. J Am Med Assoc.
1956;160(4):277–82.
49. Matevossian E, Kern H, Huser N, Doll D, Snopok
Y, Nahrig J, Altomonte J, Sinicina I, Friess H,
Thorban S.Surgeon Yurii Voronoy (1895-1961)a pioneer in the history of clinical transplantation: in memoriam at the 75th anniversary of the
rst human kidney transplantation. Transpl Int.
2009;22(12):1132–9.
50. Prasad A, Stone GW, Holmes DR, Gersh
B. Reperfusion injury, microvascular dysfunction,
and cardioprotection: the "dark side" of reperfusion.
Circulation. 2009;120(21):2105–12.
51. Harukuni I, Bhardwaj A. Mechanisms of brain
injury after global cerebral ischemia. Neurol Clin.
2006;24(1):1–21.
52. Cerra FB, Lajos TZ, Montes M, Siegel
JH. Hemorrhagic infarction: A reperfusion injury
following prolonged myocardial ischemic anoxia.
Surgery. 1975;78(1):95–104.
53. Khalil AA, Aziz FA, Hall JC.Reperfusion injury.
Plast Reconstr Surg. 2006;117(3):1024–33.
54. Farhood A, McGuire GM, Manning AM, Miyasaka
M, Smith CW, Jaeschke H. Intercellular adhesion
molecule 1 (ICAM-1) expression and its role in
neutrophil-induced ischemia-reperfusion injury in
rat liver. J Leukoc Biol. 1995;57(3):368–74.
55. Nolte D, Lehr HA, Messmer K.Adenosine inhibits
postischemic leukocyte-endothelium interaction in
postcapillary venules of the hamster. Am J Phys.
1991;261(3 Pt 2):H651–5.
56. Rashid MA, William-Olsson G. Are leukocytosis
and lipid peroxidation involved in ischemic or reperfusion injury in cardiac surgery? Thorac Cardiovasc
Surg. 1991;39(4):193–5.
57. Zimmerman BJ, Granger DN. Mechanisms
of reperfusion injury. Am J Med Sci.
1994;307(4):284–92.
58. Lazarus B, Messina A, Barker JE, Hurley JV, Romeo
R, Morrison WA, Knight KR.The role of mast cells
in ischaemia-reperfusion injury in murine skeletal
muscle. J Pathol. 2000;191(4):443–8.
59. Cuzzocrea S, Riley DP, Caputi AP, Salvemini
D. Antioxidant therapy: a new pharmaco-
17 Targeting C-Reactive Protein inInammatory Disease
https://t.me/medicina_free
185
logical approach in shock, inammation, and
ischemia/reperfusion injury. Pharmacol Rev.
2001;53(1):135–59.
60. Eisenhardt SU, Schmidt Y, Karaxha G, Iblher N,
Penna V, Torio-Padron N, Stark GB, Bannasch
H.Monitoring molecular changes induced by ischemia/reperfusion in human free muscle ap tissue
samples. Ann Plast Surg. 2012;68(2):202–8.
61. Thiele JR, Habersberger J, Braig D, Schmidt Y,
Goerendt K, Maurer V, Bannasch H, Scheichl A,
Woollard KJ, von Dobschütz E, Kolodgie F, Virmani
R, Stark GB, Peter K, Eisenhardt SU.Dissociation
of pentameric to monomeric C-reactive protein
localizes and aggravates inammation: in vivo
proof of a powerful proinammatory mechanism
and a new anti-inammatory strategy. Circulation.
2014;130(1):35–50.
62. Braig D, Kaiser B, Thiele JR, Bannasch H, Peter
K, Stark GB, Koch HG, Eisenhardt SU. A conformational change of C-reactive protein in burn
wounds unmasks its proinammatory properties. Int
Immunol. 2014;26(8):467–78.
63. Miyake Y, Yamasaki S.Sensing necrotic cells. Adv
Exp Med Biol. 2012;738:144–52.
64. Kudlackova M, Andel M, Hajkova H, Novakova
J. Acute phase proteins and prognostic inammatory and nutritional index (PINI) in moderately burned children aged up to 3 years. Burns.
1990;16(1):53–6.
65. Barrett M. The clinical value of acute phase reactant measurements in thermal injury. Scand J Plast
Reconstr Surg Hand Surg. 1987;21(3):293–5.
66. Faymonville ME, Micheels J, Bodson L, Jacquemin
D, Lamy M, Adam J, Duchateau J.Biochemical
investigations after burning injury: complement system, protease-antiprotease balance and
acute-phase reactants. Burns Incl Therm Inj.
1987;13(1):26–33.
67. Friedl HP, Till GO, Trentz O, Ward PA.Roles of histamine, complement and xanthine oxidase in thermal
injury of skin. Am J Pathol. 1989;135(1):203–17.
68. Oldham KT, Guice KS, Till GO, Ward PA.Activation
of complement by hydroxyl radical in thermal injury.
Surgery. 1988;104(2):272–9.
69. Pruchniewski D, Pawlowski T, Morkowski J,
Mackiewicz S.C-reactive protein in management of
children's burns. Ann Clin Res. 1987;19(5):334–8.
70. Kang HJ, Kim JH, Lee EH, Lee YK, Hur M, Lee
KM.Change of complement system predicts the outcome of patients with severe thermal injury. J Burn
Care Rehabil. 2003;24(3):148–53.
71. Gelfand JA, Donelan M, Hawiger A, Burke
JF. Alternative complement pathway activation
increases mortality in a model of burn injury in mice.
J Clin Invest. 1982;70(6):1170–6.
72. Ward PA, Till GO.Pathophysiologic events related
to thermal injury of skin. J Trauma. 1990;30(12
Suppl):S75–9.
73. Wan KC, Evans JH. Free radical involvement in
hypertrophic scar formation. Free Radic Biol Med.
1999;26(5-6):603–8.
74. van de Goot F, Krijnen PA, Begieneman MP, Ulrich
MM, Middelkoop E, Niessen HW.Acute inammation is persistent locally in burn wounds: a pivotal
role for complement and C-reactive protein. J Burn
Care Res. 2009;30(2):274–80.
75. Feng X, Shen R, Tan J, Chen X, Pan Y, Ruan
S, Zhang F, Lin Z, Zeng Y, Wang X, Lin Y, Wu
Q.The study of inhibiting systematic inammatory
response syndrome by applying xenogenic (porcine)
acellular dermal matrix on second-degree burns.
Burns. 2007;33(4):477–9.
76. Francois CG, Breidenbach WC, Maldonado C,
Kakoulidis TP, Hodges A, Dubernard JM, Owen
E, Pei G, Ren X, Barker JH.Hand transplantation:
comparisons and observations of the rst four clinical cases. Microsurgery. 2000;20(8):360–71.
77. Janeway CA Jr. Approaching the asymptote?
Evolution and revolution in immunology. Cold
Spring Harb Symp Quant Biol. 1989;54(Pt
1):1–13.
78. Iwasaki A, Medzhitov R. Regulation of adaptive
immunity by the innate immune system. Science.
2010;327(5963):291–5.
79. Oberbarnscheidt MH, Zeng Q, Li Q, Dai H, Williams
AL, Shlomchik WD, Rothstein DM, Lakkis FG.Nonself recognition by monocytes initiates allograft
rejection. J Clin Invest. 2014;124(8):3579–89.
80. Gallucci S, Lolkema M, Matzinger P.Natural adjuvants: endogenous activators of dendritic cells. Nat
Med. 1999;5(11):1249–55.
81. Kono H, Rock KL. How dying cells alert the
immune system to danger. Nat Rev Immunol.
2008;8(4):279–89.
82. Matas AJ, Gillingham KJ, Payne WD, Najarian
JS.The impact of an acute rejection episode on longterm renal allograft survival (t1/2). Transplantation.
1994;57(6):857–9.
83. Gewurz H, Mold C, Siegel J, Fiedel B.C-reactive
protein and the acute phase response. Adv Intern
Med. 1982;27:345–72.
84. Thompson D, Pepys MB, Wood SP. The physiological structure of human C-reactive protein
and its complex with phosphocholine. Structure.
1999;7(2):169–77.
85. Ramadan MA, Shrive AK, Holden D, Myles
DA, Volanakis JE, DeLucas LJ, et al. The threedimensional structure of calcium-depleted human
C-reactive protein from perfectly twinned crystals.
Acta Crystallogr D Biol Crystallogr. 2002;58(Pt 6 Pt
2):992–1001.
86. Shrive AK, Cheetham GM, Holden D, Myles DA,
Turnell WG, Volanakis JE, Pepys MB, Bloomer
AC, Greenhough TJ. Three dimensional structure of human C-reactive protein. Nat Struct Biol.
1996;3(4):346–54.
87. Eisenhardt SU, Thiele JR, Bannasch H, Stark GB,
Peter K. C-reactive protein: how conformational
changes inuence inammatory properties. Cell
Cycle. 2009;8(23):3885–92.
88. Lu J, Marnell LL, Marjon KD, Mold C, Du Clos
TW, Sun PD.Structural recognition and functional
Соседние файлы в папке Библиотека им академика М.И. Перельмана