A ROLE FOR C5 AND C5A-ASE IN THE ACUTE NEUTROPHIL RESPONSE TO GROUP-BSTREPTOCOCCAL INFECTIONS

Congenic C5-deficient and C5-sufficient mice were infected with group B streptococci (GBS) to determine if the polymorphonuclear leukocyte ( PMNL) chemoattractant C5a contributes to PMNL recruitment in GBS infec tion and if GBS C5a-ase reduces C5a-induced PMNL recruitment in vivo. PMNL accumulation was greater in the peritoneum and air spaces of C5-s ufficient mice than in C5-deficient mice. Administration of human C5 t o C5-deficient mice caused a significant increase in PMNL recruitment following infection with C5a-ase-negative GBS. GBS C5a-ase did not red uce PMNL accumulation in C5-sufficient mice but reduced PMNL recruitme nt in C5-deficient mice reconstituted with human C5. These data indica te that C5a is important for rapid PMNL recruitment to sites of GBS in fection and that GBS C5a-ase inactivates human, but not murine, C5a in vivo. Reduction of the acute inflammatory response by C5a-ase likely contributes to GBS virulence in human neonates.