Interaction of human monocytes, macrophages, and polymorphonuclear leukocytes with zymosan in vitro. Role of type 3 complement receptors and macrophage-derived complement.
Macrophages take up zymosan in the absence of exogenous complement via receptors for iC3b (type 3 complement receptors) acting with or without lectin-like receptors for mannosyl-fucosyl-terminated glycoconjugates. We previously provided evidence that macrophages themselves secrete complement-alternative pathway components able to opsonize zymosan locally (Ezekowitz et al., J. Exp. Med. 1984. 159:244-260). We show here that covalently bound C3 cleavage products C3b and iC3b can be eluted from zymosan particles cultivated with 36-h adherent human monocytes in the absence of serum. The ligand binding site of type 3 complement receptors is involved in macrophage-zymosan interactions as shown by inhibition studies of zymosan binding and uptake with Fab fragments of anti-C3 antibodies and monoclonal antireceptor antibodies M01 and OKM10. In contrast, antibody IB4, which binds to a receptor epitope distinct from the binding site, does not inhibit zymosan uptake. Selective modulation of macrophage receptors onto anticomplement receptor antibody and mannose-rich yeast mannan, respectively, confirms that the complement and lectin-like receptors are distinct. Human polymorphonuclear leukocytes, which express receptors for complement, but are not known to secrete complement proteins, bind and ingest only exogenously opsonized zymosan. Unopsonized zymosan is a poor trigger of respiratory burst activity in neutrophils or 7-d adherent human macrophages, but induces cell aggregation and secretion of large amounts of superoxide anion when these cells are co-cultivated in serum-free medium and challenged with zymosan. Our studies indicate that complement and/or other products synthesized by macrophages at extravascular sites could play an important role in opsonization and lysis of pathogens able to activate the alternative pathway and mediate macrophage-neutrophil collaboration in first-line host defence.
D000818:Animals; D002478:Cells, Cultured; D003176:Complement C3 / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism; D017242:Complement Factor H; D005260:Female; D037181:Lectins, C-Type; D008264:Macrophages / Q000276:immunology*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D009895:Opsonin Proteins; D011956:Receptors, Cell Surface; D011951:Receptors, Complement / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology; D015054:Zymosan
C493495:CFH protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009895:Opsonin Proteins; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D011971:Receptors, Immunologic; D017242:Complement Factor H; D015054:Zymosan