Mac-1 (CD11b/CD18) as accessory molecule for Fc alpha R (CD89) binding of IgA.
IgA, the principal ligand for FcalphaRI, exists in serum as monomeric IgA and at mucosal sites as secretory IgA (SIgA). SIgA consists of dimeric IgA linked by joining chain and secretory components. Human polymorphonuclear leukocytes (PMN) and mouse PMN transgenic for human FcalphaRI exhibited spreading and elicited respiratory burst activity upon interaction with either serum or SIgA. However, PMN devoid of the beta(2) integrin Mac-1 (Mac-1(-/-)) were unable to bind SIgA, despite expression of FcalphaRI. Consistent with this, serum IgA stimulated Mac-1(-/-) PMN oxygen radical production, in contrast to SIgA. Binding studies showed the secretory component, by itself, to interact with Mac-1-expressing PMN, but not with Mac-1(-/-) PMN. These data demonstrate an essential role for Mac-1 in establishing SIgA-FcalphaRI interactions.
Van Spriel
Annemiek B
AB
Immunotherapy Laboratory, Department of Immunology, University Medical Center, Medarex Europe, and Genmab, Utrecht, The Netherlands.
Leusen
Jeanette H W
JH
Vilé
Henriëtte
H
Van De Winkel
Jan G J
JG
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001666:Binding Sites, Antibody / Q000235:genetics; D039481:CD11b Antigen / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011961:Receptors, Fc / Q000378:metabolism*; D016897:Respiratory Burst / Q000276:immunology; D012635:Secretory Component / Q000378:metabolism
D015703:Antigens, CD; D039481:CD11b Antigen; D018821:CD18 Antigens; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D037102:Lectins; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc; D012635:Secretory Component