Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5625_Библиотеки_им_академика_М_И_Перельмана

In 1892, Pfeiffer (a disciple of the bacteriologist Koch) revealed that Vibrio cholerae produces two different toxic components: one is a heat-labile exotoxin and the other is a heat-stable endotoxin [6]. In 1945, Westphal (later the first director of the Max Planck Institute of Immunobiology and Epigenetics) reported that the active ingredi­ent of endotoxin is LPS, the outer membrane component of Gram-negative bacte­ria [6]. In 1957, the LPS terminus-acylated disaccharide, glycolipid lipid A, was reported as the active core of LPS[6]. Shiba and Kusumoto began collaborating with a German research group and submitted the correct structure of E. coli lipid A (1) (Figure4.1), and in 1985, they succeeded in the first total synthesis of E. coli lipid A (1), confirming that lipid A is the active core of endotoxin[7]. Simultaneously, Qureshi and Takayama identified the lipid A structure [8]. Shiba and Kusumoto also achieved lipid IVa (3) synthesis (Figure4.2), a precursor of E. coli lipid A[1], and found that lipid IVa (3) has an immunostimulatory effect in mice but an antag­onistic effect in humans[9]. The presence of an antagonist suggested the presence of receptors, which led to LPS receptor exploratory studies. In 1996, a breakthrough was achieved by Hoffmann, who revealed that the Toll gene, which regulates dors­oventral axis formation in Drosophila, is essential to the defense mechanism against the fungus, leading to the discovery of various innate immune recep­tors[10]. In 1997, TLRs were found to be human homologs of the Drosophila Toll protein[11], and Beutler identified TLR4 as an LPS receptor in 1998[12]. To date, 10 types of TLRs (TLR1–10) in humans and 12 types (TLR1–9, TLR11–13) in mice have been identified.