Blockade of leucocyte function-associated antigen-1 (LFA-1) decreases lymphocyte trapping in the normal pulmonary vasculature: studies in the isolated buffer-perfused rat lung

Adhesion molecules regulate the migration of lymphocytes in lymphoid and no n-lymphoid organs. In the lung, little is known about lymphocyte sticking a nd migration through the pulmonary vascular endothelium in physiological or pathological situations. Therefore the isolated buffer-perfused rat lung w as used to investigate the mobilization of lymphocytes out of the normal lu ng into the venous effluent and to the bronchoalveolar space. The lymphocyt e subset composition was characterized in the venous effluent, the lung tis sue and the bronchoalveolar lavage (BAL) using immunocytology. Lymphocytes continuously left the normal lung at a total of 5.0 +/- 0.7 x 10(6) cells w ithin the first hour of perfusion. The injection of 200 x 10(6) lymphocytes via the pulmonary trunk increased the venous release of lymphocytes by 170 %. To investigate the effect of LFA-1 and CD44 on the adhesion of lymphocyt es to the pulmonary endothelium, lymphocytes preincubated with an anti-LFA- 1 MoAb, which blocks the interaction of LFA-1 and intercellular adhesion mo lecule-1 (ICAM-1), or lymphocytes preincubated with an anti-CD44 MoAb, were injected. The injection of LFA-1-blocked lymphocytes led to an increase by 70% of injected cells recovered in the perfusate within the first hour, wh ereas anti-CD44 treatment of injected lymphocytes had no effect. The LFA-1- blocked lymphocytes showed higher numbers of T and B cells in the effluent. Thus, the present experiments demonstrate that LFA-1 influences the trappi ng of lymphocytes in the vasculature of the healthy rat lung.