Activation of the alternative complement pathway by a streptococcal lipoteichoic acid

Abstract

A glycerol lipoteichoic acid antigen from Streptococcus pyogenes 1-RP41 was found by rabbit erythrocyte hemolytic assay to activate the alternative complement pathway in human sera. Over a narrow concentration range of the teichoic acid, complement consumption was dose dependent, whereas at higher concentrations of the acid complement consumption could not be detected.

Effects of a streptococcal lipoteichoic acid on complement activation in vitro

“…The resuits reported here showed that LTA from S. mutans caused a dose-dependent conversion of C3 when tested in solution (Figs. 1, 2), The finding complies with results from other studies, based on hemolytic assays (Fiedel & Jackson 1978, Wilkinson et al, 198i, Hummell et al 1985, Loos et al 1986). Degradation of C3 yields split products with important inflammatory potential.…”

“…The functional capabilities of the two activation pathways were evaluated by lysing RBCs, The results (Table 2) cor-responded to those obtained with the quantitative assays (Fig, 2, Table I), The empirical data obtained with LPS were in accordance with those reported by Morrison & Kline (1977). The borderline statistically significant AHjo values, found for LTA were reminiscent of other work reported; Fiedel & Jackson (1978) found no complement consumption at high doses of LTA. Equally, neither did pneumococcal LTA induce the alternative pathway when examined in solution by functional assays (Hummell et al 1985).…”

“…Since most LTAs cross-react immunoiogically through their common glycerol-phosphate backbone (Knox &Wicken 1975), some antibody-dependent complement activation might take place in the periodontal milieu. Third, it is generally held that LTAs and LPSs are potent activators of the alternative pathway (Fiedel & Jackson 1978, Hummel! et al 1985, i.e., they provide binding sites for deposition of C3b and shield the C3 convertases generated from the regula- tory proteins.…”

“…Early studies showed that several Gram-positive bacteria, including streptococci from dental plaque, activated serum complement in vitro through the two known pathways (Tsai et al, 1977). Fiedel & Jackson (1978) showed that, over a narrow dose range, streptococcal LTA was anti-complementary and inferred that LTA primarily activates the alternative pathway in human sera. When pneumococcal LTA was bound to the surface of sheep erythrocytes (RBCs), it activated the alternative pathway, but was inactive when tested in solution (Hummell et aJ, 1985).…”

Stimulation of lysosomal enzyme release from macrophages by lipoteichoic acid

“…It was also noted that the various substances that induced chronic inflammation such as dextran sulphates, are not readily degradable, so that they would persist in macrophages, and also have the "polymeric acid structural requirements" for activating complement by the alternate pathway (Page, Davies & Allison 1978). In this context it is relevant that LTA is a high molecular weight acidic polymer, that mammalian enzymes for its degradation are not known, and that it has recently been shown to activate the alternate complement pathway (Fiedel & Jackson 1978). The complement cleavage pro-duct C3b is capable of causing selective release of acid hydrolases from macrophages (Schorlemmer & Allison 1976) and thus provides an alternate mechanism for the mode of action in vivo of LTA and also of LPS.…”