Phagocytic function of polymorphonuclear leukocytes and the RES in endotoxemia.
The reticuloendothelial system (RES) and the polymorphonuclear leukocytes (PMNs) are thought to play a major role in defense against sepsis. Disturbances in the function of these two phagocytic systems during a septic event is associated with the development of lung capillary injury. Endotoxemia is said to lead to similar changes. Our study examined the function of the RES and PMNs after bolus injection of endotoxin (2 micrograms/kg BW) in a standardized sheep model. For up to 24 hr after endotoxin, blood samples were drawn and PMN function was followed by chemiluminescence, chemotaxis, and adherence as well as the phagocytosis and killing of bacteria. RES function was determined by the blood clearance of a labeled Tc99 colloid. We found an increase of RES clearance directly after endotoxin. Chemotaxis, phagocytosis, and killing were reduced. Adherence was increased. Chemiluminescence peak maximum (CLPM), representing the metabolic activity of the PMNs, was initially increased but shortly thereafter showed a significant decline (at 1 hr: 0.52 +/- 0.13 X 10(6) cpm with P less than 0.05 compared to baseline). The chemiluminescence peak time (CLPT), a measure of membrane receptor function, was significantly reduced (10.0 +/- 2.2 min with P less than 0.001 compared to baseline). Endotoxin led to a reduction of intracellular PMN functions (phagocytosis, killing, CLPM) within 1 hr. Membrane localized functions (adherence, CLPT) were increased. The changes in PMN function might be the reason for the development of lung capillary injury, in spite of undisturbed RES clearance.
D000818:Animals; D001770:Blood Bactericidal Activity; D002634:Chemotaxis, Leukocyte; D004731:Endotoxins / Q000097:blood*; D005260:Female; D007958:Leukocyte Count; D008163:Luminescent Measurements; D012157:Mononuclear Phagocyte System / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis; D011669:Pulmonary Wedge Pressure; D018805:Sepsis / Q000276:immunology*; D012756:Sheep
D004731:Endotoxins