The role of CD11/CD18 integrins in the reverse passive Arthus reaction in rat dermal tissue.
The CD11/CD18 leukocyte integrins are necessary for tissue localization of neutrophils, an early requisite event in inflammation. We have analyzed the contribution of CD11a/CD18 and CD11b/CD18 to local neutrophil accumulation and tissue injury in the reverse passive Arthus reaction in the rat dermis. Experimental groups comprised animals that received an intravenous infusion of (1) recombinant neutrophil inhibitory factor (NIF), a hookworm-derived antagonist of CD11b/CD18; (2) monoclonal antibody to CD11a/CD18 (TA-3); (3) a combination of these agents; (4) a monoclonal antibody to CD18 (WT.3); or (5) saline. Administration of recombinant NIF or anti-CD11a/CD18 monoclonal antibody alone produced a slight reduction in neutrophil accumulation but did not affect edema formation. In contrast, a combination of these antagonists yielded a significant reduction in neutrophil accumulation and a modest reduction in edema, equivalent to levels observed with either anti-CD18 antibodies or animals that were rendered neutropenic. These results indicate that neutrophil infiltration in rat dermal tissue in the reverse passive Arthus reaction is dependent predominantly on the leukocyte integrins CD11a/CD18 and CD11b/CD18 and that either of these integrins is sufficient for neutrophil trafficking in this inflammatory setting.
Rote
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Department of Molecular Pharmacology, Corvas International, Inc., San Diego, CA 92121, USA.
Dempsey
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E
Maki
S
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Vlasuk
G P
GP
Moyle
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001183:Arthus Reaction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D018845:CD11 Antigens / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D018821:CD18 Antigens / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D003872:Dermatitis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D004487:Edema / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006023:Glycoproteins / Q000494:pharmacology; D015801:Helminth Proteins / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D006023:Glycoproteins; D015801:Helminth Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C086581:NIF protein, Ancylostoma caninum