SOLUBLE FC-GAMMA-RECEPTOR-TYPE-III (FC-GAMMA-RIII, CD16) TRIGGERS CELL ACTIVATION THROUGH INTERACTION WITH COMPLEMENT RECEPTORS

The type IIl-B Fc gamma receptor (Fc gamma RIII-B) is a glycosyl-phosp hatidylinositol-linked receptor found on human neutrophils, A soluble form of Fc gamma RIII-B (sCD16) corresponding to the extracellular reg ion of the receptor circulates in plasma, In the present work, we have identified membrane receptors for sCD16, Soluble CD16 bound to CR3 (C D11b/CD18)- and CR4 (CD11c/CD18)-positive leukocytes and cell lines, t he labeling was inhibited by anti-CD11b, CD11c or CD18 mAbs, and the u p-regulation of CR3 and CR4 led to an increased fixation of sCD16, Tra nsfected eukaryotic cells expressing recombinant CD11b/CD18 or CD11c/C D18 heterodimers but not those expressing CD11a/CD18 bound sCD16, More over, the lectin-like binding site of CR3 is probably involved in the interaction with sCD16, as suggested by inhibition studies using mAbs against CR3 or sugars such as N-acetyl D-glucosamine, alpha- or beta-m ethyl D-glucoside, alpha- or beta-methyl D-mannoside, or zymosan. Thus , the complement receptors CR3 and CR4 are membrane receptors for sCD1 6, Through this interaction, sCD16 induces a CR3-dependent production of IL-6 and IL-8 by monocytes, These results suggest that sCD16 plays a regulatory role in inflammatory processes and provide a molecular ba sis for the interaction between Fc gamma RIII-B and CR3 described on t he cell membrane.