Soluble Fcgamma receptor type III (FcgammaRIII, CD16) triggers cell activation through interaction with complement receptors.
The type III-B Fcgamma receptor (FcgammaRIII-B) is a glycosyl-phosphatidylinositol-linked receptor found on human neutrophils. A soluble form of FcgammaRIII-B (sCD16) corresponding to the extracellular region of the receptor circulates in plasma. In the present work, we have identified membrane receptors for sCD16. Soluble CD16 bound to CR3 (CDllb/CD18)- and CR4 (CDllc/CD18)- positive leukocytes and cell lines, the labeling was inhibited by anti-CD11b, CD11c or CD18 mAbs, and the up-regulation of CR3 and CR4 led to an increased fixation of sCD16. Transfected eukaryotic cells expressing recombinant CD11b/CD18 or CD11c/CD18 heterodimers but not those expressing CD11a/CD18 bound sCD16. Moreover, 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-methyl D-glucoside, alpha- or beta-methyl D-mannoside, or zymosan. Thus, the complement receptors CR3 and CR4 are membrane receptors for sCD16. 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 basis for the interaction between FcgammaRIII-B and CR3 described on the cell membrane.
Galon
J
J
Laboratory of Cellular and Clinical Immunology, INSERM Unit 255, Curie Institute, Paris, France.
Gauchat
J F
JF
Mazières
N
N
Spagnoli
R
R
Storkus
W
W
Lötze
M
M
Bonnefoy
J Y
JY
Fridman
W H
WH
Sautès
C
C
D000911:Antibodies, Monoclonal / Q000276:immunology; D018845:CD11 Antigens / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D015850:Interleukin-6; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D017452:Receptors, IgG