Inhibition of complement-mediated opsonization and phagocytosis of Streptococcus pyogenes by D fragments of fibrinogen and fibrin bound to cell surface M protein.

The biological effects of the binding of fibrin(ogen) degradation products to M protein-bearing group A streptococci were investigated. Type 24 group A streptococci bind fibrinogen degradation products of the D family, but not fragment E. Binding appears to be mediated by M protein, since a large peptide of this molecule (pep M24) bound to fragments containing the terminal domains of the fibrinogen molecule (D, X, and Y), but not fragment E, and pep M24 inhibited the binding of digested fibrinogen to streptococcal cells. An M protein-binding site occurs on fragment D3 and, therefore, differs from several functional sites present on D1 but not D3, including the fibrin polymerization site, the two gamma chain crosslink sites, and the bindings sites for platelet fibrinogen receptor, staphylococcal clumping factor, and ionized calcium. Bound fibrinogen degradation products prevented deposition of C3 on the streptococcal cell surface, and, in consequence, prevented phagocytosis by neutrophils in nonimmune blood. The average affinity of D fragments for the streptococcal cell surface was approximately 30 times lower than that of native fibrinogen, and a terminal plasmic digest was approximately 50 times less potent in inhibiting opsonization by C3. However, physiologic concentrations of digested fibrinogen sufficed to inhibit opsonization and phagocytosis completely. Digests of crosslinked fibrin clot also inhibited opsonization, although slightly less effectively than did fibrinogen digests. The antiopsonic effect of fibrin(ogen) degradation products may be relevant to circumstances in which fibrin(ogen)olysis is occurring, e.g., exudation and suppuration.