EFFECTS OF RECOMBINANT BACTERICIDAL PERMEABILITY-INCREASING PROTEIN [RBPI(23)] ON NEUTROPHIL ACTIVITY IN BURNED RATS/

Bactericidal/permeability-increasing protein (BPI) is a neutrophil gra nule protein with potent bactericidal and lipopolysaccharide (LPS)-neu tralizing activities. The purpose of this study was to determine if a human recombinant BPI product, rBPI(23), would influence neutrophil (P MN) sequestration into various tissues in a rat burn injury model, Leu kosequestration may produce local tissue injury from proteases and hig h-energy oxygen species released from PMNs. Rats received tracheostomy and venous cannulation, then received 17 to 20% total body surface ar ea full-thickness contact burns and resuscitation with 20 mL of intrap eritoneal saline. Ten mg/kg body weight rBPI(23) in saline was given b y intravenous injection immediately after burn injury, followed by int ravenous doses of 2 mg/kg at 2 and 4 hours. Control animals received i ntravenous saline only. PMN retention in lung, liver, spleen, gut, ski n, muscle, kidney, and brain tissues was determined by removing (befor e burn injury) and differentially radiolabeling PMNs (In-111) and eryt hrocytes (Cr-51), reinfusing cells 4.5 hours after burn injury, and me asuring tissue radioactivity 30 minutes later. Edema was estimated by measuring extravasated I-125-labeled albumin in the various tissues, 3 0 minutes after injection. Peripheral blood PMNs were analyzed for int racellular H2O2 content by flow cytometry using a fluorescent dye that reacts with H2O2. Radioisotope studies demonstrated significant (p < 0.05) leukosequestration into lung, liver, gut, kidney, and skin tissu es at 5 hours after burn injury. Tissue edema, manifested by radiolabe led albumin retention, was not observed in any tissues. Postburn PMN d eposition in lungs and skin was decreased (p < 0.05) by the immediate administration of rBPI(23) after burn injury. Flow cytometry showed in creased intracellular H2O2 content in peripheral blood PMNs 5 hours af ter burn injury (p < 0.05), which was unaffected by administration of rBPI(23). Since sequestration of metabolically active PMNs may induce tissue injury, therapies that block leukosequestration after burn inju ry may improve clinical outcomes by limiting remote tissue injury.