Dissemination of gonococcal infection is associated with delayed stimulation of complement-dependent neutrophil chemotaxis in vitro.
Gonococci isolated from patients with uncomplicated gonorrhea or disseminated infection were examined for their ability to stimulate neutrophil chemotaxis in vitro. A neutrophil chemotactic response was not observed when as many as 10(9) colony-forming units of gonococci were incubated in buffer alone. However, a striking response was observed when 4 x 10(7) colony-forming units were incubated in 10% pooled normal human serum. Activation of complement was required for chemotaxis as demonstrated by complement consumption and failure of chemotactic activity generation in serum treated with heat or EDTA. Chromatography of activated serum demonstrated a single peak of chemotactic activity with an apparent molecular weight of 15,000 and was shown to be due to C5a. Examination of the kinetics of chemotactic factor generation demonstrated that local isolates stimulated a rapid response (about 60% maximal in 5 min), whereas the response to disseminated isolates was delayed (50% maximal in 20 to 30 min). Chemotactic activity generated by both types of isolates was suppressed at early time periods in agammaglobulinemic serum, indicating that immunoglobulins contribute to the generation of activity. Both pathways of complement activation were utilized by the two types of gonococci, but there was preferential dependence on the alternative pathway for disseminated strains and on the classical pathway for local isolates. We suggest that delayed stimulation of complement-dependent neutrophil migration may account in part for the infrequency of genital symptoms and may contribute to the mechanism of dissemination in patients with systemic gonococcal infection.
D002634:Chemotaxis, Leukocyte; D003182:Complement C5 / Q000502:physiology*; D015936:Complement C5a; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D005260:Female; D006069:Gonorrhea / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology; D007700:Kinetics; D008297:Male; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D009504:Neutrophils / Q000502:physiology
D003182:Complement C5; D007136:Immunoglobulins; D015936:Complement C5a