MONOCLONAL-ANTIBODIES TO P-SELECTIN AND E -SELECTIN FOR THERAPEUTIC INTERFERENCE WITH LEUKOCYTE SEQUESTRATION IN STRIATED-MUSCLE OF THE BALB C-MOUSE AFTER ENDOTOXINEMIA/

The functional role of the leukocyte adhesion molecules P-selectin and E-selectin in endotoxinemia was analyzed in the microcirculation mode l of the Balb/c-mouse. Injection of endotoxin (2 mg kg(-1) KG iv, S. a bortus-equi) led to a significant decrease of rolling leukocytes 1 h a nd 5 h after injection, followed by a significant increase 8 h and 24 h after administration. Leukocyte rolling and sticking were significan tly reduced by anti-P-selectin mAb 1 h after endotoxin injection, whil e leukocyte rolling was reduced at 8 h post-endotoxin by both anti-P-s electin and anti-E-selectin mAb. At 8 h and 24 h post-endotoxin, the f urther increase in leukocyte sticking was only seen in animals treated with anti-E-selectin mAb. These results imply the additive blockade o f P- and E-selectin in endotoxinemia as useful therapeutic strategy.