NEUTROPHIL CD18 EXPRESSION AND BLOCKADE AFTER TRAUMATIC SHOCK AND ENDOTOXIN CHALLENGE

Objective The expression of the leukocyte CD18 adhesion complex on pol ymorphonuclear leukocytes (PMNs) was measured, and the physiologic eff ects of blockade of the complex were studied after trauma and sepsis. Summary Background Data Margination of PMNs occurs early during inflam mation and depends, in part, on expression of the CD18 adhesion comple x. Blockade of this adherence complex can reduce PMN-mediated damage. This study tests the hypothesis that PMN activation after resuscitated trauma produces an occult endothelial injury that increases the vulne rability to a delayed inflammatory stimulus. Methods Anesthetized (fen tanyl) mongrel pigs were sham injured or fluid resuscitated from soft tissue injury + 35% hemorrhage. Systemic blood was collected at 24-hou r intervals from awake animals. The CD18 density on circulating PMNs w as determined with flow cytometry using mean channel fluorescence (MCF ). The CD18 receptors were blocked with monoclonal antibodies either i mmediately before trauma or immediately before an endotoxin (lipopolys accharide [LPS]) challenge that was administered to all groups 3 days after the shock episode. Bronchoscopy was performed before trauma, pre -LPS, and post-LPS, and protein content was measured in bronchoalveola r lavage (BAL). Results Mean channel fluorescence was reduced on PMNs for 48 hours in animals with trauma versus animals with sham injuries. Anti-CD18 therapy produced higher circulating PMN counts compared wit h nontreated sham or shock groups. The incremental rise of BAL protein after shock was prevented with anti-CD18; the increment after LPS was attenuated. Anti-CD18 was administered before trauma and reduced the fluids necessary to maintain cardiac filling pressures after LPS. Conc lusions These data suggest that PMNs are activated after resuscitation from traumatic shock and that these cells produce an endothelial inju ry that may increase the vulnerability to a septic challenge.