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 β2 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, C5a(des Arg)), IL-1 or endotoxin (P < 0.01) and suppressed T lymphocyte migration to dermal DTH, IFN-γ, LPS, and poly-I:C-induced inflammation by 60-80%. Anti-MAC-1 (OX-12) 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. © 1993 Academic Press, Inc.