LFA-1 AND 1-SELECTIN REGULATION OF RECIRCULATING LYMPHOCYTE TETHERINGAND ROLLING ON LUNG MICROVASCULAR ENDOTHELIUM

Recirculating lymphocytes migrate into areas of lung inflammation by b inding to microvascular endothelium and transmigrating into extravascu lar tissue. In this report, we examined the multiple-step paradigm usi ng a unique system: recirculating lymphocytes from sheep peripheral ly mphatics adhering to activated lung microvascular endothelium in condi tions of physiologic flow. Video microscopy demonstrated that recircul ating lymphocytes formed abrupt adhesions, without requisite rolling, on the lung microvascular endothelial cells. Lymphocyte velocity was u nchanged within 100 ms of the development of firm adhesions. To dissec t the adhesion mechanism, the lymphocytes were pretreated with anti-LF A-1 or anti-L-selectin monoclonal antibody (mAb). Both mAb decreased t he incidence of firm adhesions. The mechanism of this inhibition was i nvestigated using time-lapse topographic reconstructions of cell movem ent after pretreatment with mAb. Time-lapse analysis of the movement o f lymphocytes pretreated with anti-LFA-1 mAb suggested that abortive a dhesion was manifested by a characteristic saltatory movement and a su stained reduction in cell velocity (rolling) to < 25 mu m/s. In contra st, abortive adhesions of lymphocytes pretreated with anti-L-selectin mAb demonstrated transient arrest (tethering) but minimal rolling befo re resumption of baseline velocity in the flow stream. These observati ons provide insights into selectin and integrin regulation of lymphocy te transmigration into the lung. Further, the results of mAb inhibitio n suggest that the mechanism of lymphocyte migration may have some uni que features not observed in studies of neutrophil transmigration.