The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23.
The vitronectin receptor, alphavbeta3 integrin, plays an important role in tumor cell invasion, angiogenesis, and phagocytosis of apoptotic cells. CD47, a member of the multispan transmembrane receptor family, physically and functionally associates with vitronectin receptor (VnR). Although vitronectin (Vn) is not a ligand of CD47, anti-CD47 and beta3 mAbs suppress Vn, but not fibronectin (Fn) binding and function. Here, we show that anti-CD47, anti-beta3 mAb and Vn, but not Fn, inhibit sCD23-mediated proinflammatory function (TNF-alpha, IL-12, and IFN-gamma release). Surprisingly, anti-CD47 and beta3 mAbs do not block sCD23 binding to alphav+beta3+ T cell lines, whereas Vn and an alphav mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds alphav+beta3+/CD47(-) cell lines, but coexpression of CD47 increases binding. Moreover, sCD23 binds purified alphav protein and a single human alphav chain CHO transfectant. We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.
Laboratoire Allergie, Centre de recherch¿e Louis-Charles Simard, Pavillon Notre-Dame, Centre Hospitalier Université de Montréal (CHUM), Montreal, Quebec H2L 4M1, Canada.
P
P
Hermann
M
M
Armant
E
E
Brown
M
M
Rubio
H
H
Ishihara
D
D
Ulrich
R G
RG
Caspary
F P
FP
Lindberg
R
R
Armitage
C
C
Maliszewski
G
G
Delespesse
M
M
Sarfati
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D039564:Integrin alphaV; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D015846:Monokines / Q000096:biosynthesis; D017455:Receptors, IgE / Q000378:metabolism*; D019030:Receptors, Vitronectin / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D039564:Integrin alphaV; D015846:Monokines; D017455:Receptors, IgE; D019030:Receptors, Vitronectin; D018664:Interleukin-12; D007371:Interferon-gamma