Activation of neutrophil function via CD66: differential effects upon beta 2 integrin mediated adhesion.
To further define the role of CD66 glycoproteins in the regulation of neutrophil function, we analysed the effects of a CD66 monoclonal antibody, Kat4c, which recognizes an epitope present on AB domains of CD66a, CD66b and CD66c. Intact Kat4c and F(ab')2 fragments were found to augment fMLP-induced oxidation of 1,2,3-dihydrorhodamine (oxidant species production) and beta 2 integrin-mediated adhesion to fibrinogen but did not promote beta 2 integrin-mediated binding of albumin coated latex beads. Since the latter assay is a sensitive indicator of neutrophil CD11b/CD18 functional activation, these results imply CD66 may exert differential effects upon beta 2 integrin activity. Neutrophil oxidant species production and spreading on fibrinogen substrates were further potentiated by cross-linking of Kat4c F(ab')2, in keeping with the suggestion that ligation of CD66 regulates neutrophil function. However, although intact Kat4c promoted beta 2 integrin-dependent homotypic neutrophil adhesion, F(ab')2 fragments were without effect, implying a role for Fc receptors in this effect which has previously been attributed to CD66. Together these data define more clearly the role of CD66 in regulation of neutrophil function and further suggest that augmented beta 2 integrin-mediated adhesion following CD66 ligation occurs independently of affinity regulation.
Ruchaud-Sparagano
M H
MH
Rayne Laboratory, Respiratory Medicine Unit, University of Edinburgh Medical School, U.K.
Stocks
S C
SC
Turley
H
H
Dransfield
I
I
D000911:Antibodies, Monoclonal / Q000502:physiology*; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D018845:CD11 Antigens / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D008863:Microspheres; D018375:Neutrophil Activation / Q000502:physiology; D009504:Neutrophils / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018845:CD11 Antigens; D018821:CD18 Antigens; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G