The inhibitory effect of dexamethasone on lymphocyte adhesion molecule expression and intercellular aggregation is not mediated by lipocortin 1

Glucocorticoids exert their anti-inflammatory activity through multiple pat hways which include the inhibition of cell adhesion events. The glucocortic oid-induced protein lipocortin 1 (LC1) has reported anti-inflammatory prope rties and has been proposed as a putative mediator of the anti-inflammatory effects of glucocorticoids. The role of LC1 in mediating the glucocorticoi d inhibition of lymphocyte adhesion and cell adhesion molecule (CAM) expres sion was investigated in vitro using a microaggregation assay, flow cytomet ry and confocal microscopy. Lymphocytes stimulated for 96 h with plastic-bo und OKT3 antibody showed significant increases in LFA-1 and CD2 expression. Dexamethasone (DEX; 10(-6) m) inhibited this increase but the neutralizing anti-LC1 MoAb 1A (5 mu g/ml) failed to reverse the DEX effect; neither was purified human LC1 (50 x 10(-9) m) able to inhibit CAM expression. The bio logical activity of the LC1 was confirmed by its ability to suppress monocy te phagocytosis and respiratory burst in response to bovine serum albumin ( BSA)-anti-BSA complexes. OKT3 stimulation of cultured mononuclear cells res ulted in intercellular aggregation, scored microscopically using a visual i ndex. This aggregation was completely reversed by 10(-6) m DEX but unaffect ed by LC1 (50 x 10(-9) m). Significant intracellular expression of lymphocy te LC1 was observed using the anti-LC1 MoAb 1B in saponin-permeabilized cel ls. Distribution of LC1 had a diffuse, cytoplasmic pattern. LC1 expression was reduced following 3 h treatment with 10(-6) m DEX. These findings indic ate that the DEX effects on lymphocyte adhesion and CAM expression are not mediated by LC1. Thus the reported in vivo effects of LC1 on leucocyte adhe sion and transmigration probably occur through functional/conformation chan ges of surface CAM, rather than by alteration in expression.