Selected antibodies to leukocyte common antigen (CD45) inhibit human neutrophil chemotaxis.
The CD45 Ag family is a group of high m.w. glycoproteins that are expressed on the plasma membranes of all leukocytes. CD45 has protein tyrosine phosphatase activity and appears to regulate signal transduction and lymphocyte activation by specific association with receptor molecules on T and B lymphocytes. However, little is known about CD45 function in neutrophils (PMN). In this study, PMN were incubated with CD45 mAb and tested for their chemotactic responses to four unrelated chemo-attractants: FMLP, leukotriene B4 (LTB4), recombinant human C5a (C5a), and recombinant human neutrophil-activating protein-1, recently designated IL-8. A panel of CD45 mAb including an IgM mAb, AHN-12.1, and six IgG1 mAb, AHN-12, AHN-12.2, AHN-12.3, AHN-12.4, HLe-1, and KC56(T200), were tested for their effects on PMN chemotaxis. PMN chemotaxis was evaluated with two different membrane assays; one assay quantified the total number of migrating PMN and the other assayed the leading front of migrating PMN. AHN-12.1 and KC56(T200) significantly inhibited PMN chemotaxis to LTB4 and C5a. AHN-12.1 slightly inhibited PMN chemotaxis to FMLP, but KC56(T200) did not. In contrast, AHN-12 and HLe-1 did not significantly inhibit PMN chemotaxis to any of the chemoattractants. None of the CD45 mAb inhibited PMN chemotaxis to neutrophil-activating protein-1/IL-8. None of the CD45 mAb inhibited PMN superoxide production. These results suggest that PMN CD45 epitopes may interact with LTB4 and C5a receptor-associated molecules and regulate chemotactic responses.
Harvath
L
L
Division of Blood and Blood Products, Food and Drug Administration, Bethesda, MD 20892.
Balke
J A
JA
Christiansen
N P
NP
Russell
A A
AA
Skubitz
K M
KM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000032:analysis / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D005260:Female; D006649:Histocompatibility Antigens / Q000032:analysis / Q000276:immunology*; D006801:Humans; D017493:Leukocyte Common Antigens; D016256:Lewis X Antigen; D051379:Mice; D008807:Mice, Inbred BALB C; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D006649:Histocompatibility Antigens; D016256:Lewis X Antigen; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D017493:Leukocyte Common Antigens