Involvement of LFA-1/ICAM-1 Pathway in Inflammatory Process. Effect of in vivo treatment of monoclonal antibodies on adjuvant arthritis and carrageenan induced pleurisy in rats.

Intercellular adhesion molecule 1 (ICAM-1), one of the ligands for leukocyte function-associated antigen 1 (LFA-1), plays important roles both in inflammation and in immune responses.In order to directly examine the role of ICAM-1/LFA-1 pathway in inflammatory process, we investi-gated the effect of in vivo administration of monoclonal antibodies on inflammatory models in rats. In adjuvant arthritis which is a chronic inflammatory model, both 1 A 29 (anti-rat ICAM-1) and WT-1 (anti-rat CD 11a) exerted a very strong suppressive effect on the development of arthritis. These monoclonal antibodies also suppressed the increase in serum sialic acid content in arthritic rats. Suppression of inflammatory reaction by monoclonal antibodies was also observed in rat carrageenan induced pleurisy. Flow cytometric analysis revealed that infiltrated neutrophils in pleural cavity expressed CD ha, CD 11b, CD 11c and CD 18. Administration of 1 A 29, WT-1 or WT-3 (anti-rat CD 18) significantly inhibited neutrophil extravasation into pleural cavity. These monoclonal antibodies also inhibited protein exudate into pleural cavity. However, OX 42, which was reported to recognize a common epitope shared by CD 11b and CD 11c, had no significant effect.These results clearly indicate that ICAM-1/LFA-1 pathway is involved in the pathogenesis of adjuvant arthritis and have a significant role in neutrophil extravasation in carrageenan induced pleurisy.