ROLE OF LEUKOCYTE ADHESION MOLECULES IN LUNG AND DERMAL VASCULAR INJURY AFTER THERMAL TRAUMA OF SKIN

Acute second degree thermal injury of rat skin involving 25 to 30% tot al body surface of anesthetized rats results at 4 hours in evidence of vascular injury both locally (in skin) and remotely (involving lung). The neutrophil dependency for both types of injury has now been estab lished. Monoclonal antibodies to various adhesion molecules have been used to define the requirements for these molecules in the development of vascular injury. In dermal vascular injury, a requirement for Mac- 1 (CD11b/CD18) but not for leukocyte function-associated antigen-1 (LF A-1, CD11a/CD18) has been established. In this model requirements have also been demonstrated for intercellular adhesion molecule-1 (ICAM-1) and E- and L-selectin but not for very late arising antigen-4 (VLA-4) or P-selectin. With respect to lung vascular injury, dual requirement s for both leukocyte function-associated antigen-1 and Mac-1 were foun d as well as for ICAM-1 and E- and L-selectin but not for VLA-4 and P- selectin. In the lung, there was a close correlation between neutrophi l content of the tissue (as assessed by myeloperoxidase) and the effec ts of protective interventions (directed against blocking of adhesion molecules). These data emphasize the roles of beta 2 integrins, select ins (L and E), and ICAM-1 in events that lend to neutrophil-mediated v ascular injury of dermis and lung after thermal trauma to skin