Clustering of neutrophil leucocytes in serum: possible role of Clq-containing immune complexes

SUMMARY Clustering activity for neutrophil granulocytes was generated in pooled normal human serum (NHS) by incubation of the serum with preformed IgG aggregates, but not in heat-treated NHS (56°C, 30 min), indicating that the function was complement-dependent. Judging from results of experiments with complement-deficient sera, and serum depleted of Clq, factor D and properdin, recruitment of the complement system beyond Cl was not required for induction of the activity. Zymosan treatment of NHS resulted in some neutrophil clustering activity, but recombinant C5a had a limited effect. Clq added to heat-treated NHS in conjunction with preformed IgG aggregates supported neutrophil clustering in a dose-dependent manner. The serum Clq inhibitor, a chondroitin 4-sulphate proteoglycan known to interact with the collagenous part of Clq, clearly reduced neutrophil clustering in heat-treated NHS supplemented with Clq and IgG aggregates. The Clq inhibitor also reduced the inherent neutrophil clustering activity of some sera from patients with systemic lupus erythematosus (SLE). Neutrophil clustering activity in SLE serum was earlier shown to be inversely related to the number of circulating neutrophils in vivo. Although the precise mechanisms remain unclear, we propose that Clq-containing immunoglobulin complexes mediate neutrophil clustering through Clq receptors, and that this might contribute to pathogenesis of immune complex diseases such as SLE.