PREVENTING THE INFILTRATION OF LEUKOCYTES BY MONOCLONAL-ANTIBODY BLOCKS THE DEVELOPMENT OF PROGRESSIVE ISCHEMIA IN RAT BURNS

Tissue loss as a consequence of thermal trauma occurs in two stages. T here is immediate necrosis in tissues directly killed by the thermal e nergy, followed by a delayed secondary necrosis in neighboring tissues . The infiltration of neutrophils into traumatized tissues is a hallma rk of the inflammatory response. Neutrophils have the machinery to kil l invading microorganisms, but these same weapons have the capacity to destroy the host's viable tissues as well. Leukocyte infiltration req uires their adherence to the vascular endothelial cell surface. Maskin g these adhesion sites on neutrophils will block the adhesion of neutr ophils to the endothelium. A monoclonal antibody (mAb) was developed t o guinea pig leukocyte adhesion sites CD11b/CD18, and this mAb cross-r eacts with rat leukocytes, blocking their adherence. Rats received a ' 'comb burn'' composed of four rectangular full-thickness burns placed in a row and separated by three areas left unburned. The four individu al burns convert into a single large wound because the blood flow to t he interspaces was terminated, blood vessels were occluded, and leukoc ytes were present in the extravascular space. The systemic administrat ion of the mAb (50 to 150 mu l) immediately following a comb burn prom oted the survival of the interspace, demonstrated by the prevention of loss of blood flow by laser Doppler monitoring, maintained patent ves sels by latex vascular casts, blocked extravascular migration of neutr ophils histologically at 2 hours, and limited the tissue loss to the o riginal four burns.