A major portion of polymorphonuclear leukocyte and T lymphocyte migration to arthritic joints in the rat is via LFA-1/MAC-1-independent mechanisms.
The importance of the leukocyte CD11/CD18 beta 2 integrins for leukocyte adhesion and for leukocyte migration to inflamed tissues is well recognized. However, the role of CD11/CD18 molecules and their subtypes, such as LFA-1 and MAC-1, in leukocyte migration to arthritis is not known. Here we report the effects of a new monoclonal antibody (mAb) TA-3, which recognizes and blocks rat LFA-1 (CD11a/CD18), on the migration of 51Cr-labeled rat blood polymorphonuclear leukocytes (PMNL) and 111In-labeled spleen T lymphocytes into the inflamed joints of rats with adjuvant arthritis and to dermal inflammation. The mAb MRC OX-42, which reacts with and blocks rat MAC-1 (CD11b/CD18), was also evaluated. In established arthritis, iv anti-LFA-1 (TA-3) inhibited, up to 50% (P < 0.006) of PMNL accumulation in the talar and metatarsal joints but had no effect on T lymphocyte migration to the joints. In the same animals, anti-LFA-1 partially (35-50%) inhibited PMNL accumulation in acute dermal inflammation induced by zymosan-activated serum (ZAS, C5ades Arg), IL-1 or endotoxin (P < 0.01) and suppressed T lymphocyte migration to dermal DTH, IFN-gamma, LPS, and poly-I:C-induced inflammation by 60-80%. Anti-MAC-1 (OX-42) by itself had no effect on PMNL migration. Anti-MAC-1 combined with anti-LFA-1 did not inhibit PMNL or T lymphocyte migration to joints any more than anti-LFA-1 alone. However, the addition of anti-MAC-1 to anti-LFA-1 further inhibited PMNL migration to acute dermal inflammation by up to 90%. These findings demonstrate that LFA-1 on PMNL plays a major role in PMNL migration but not in T cell migration to arthritic joints. MAC-1 on PMNL appears less important. Furthermore, while LFA-1 and MAC-1 on PMNL and LFA-1 on T lymphocytes mediate much of the migration to dermal inflammation, the migration of these cells to arthritis has a major LFA-1/MAC-1-independent component.
Issekutz
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Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
Issekutz
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D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008297:Male; D009504:Neutrophils / Q000166:cytology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000166:cytology*
D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen