Neutrophils and neutrophil products do not mediate pulmonary hemodynamic effects of endotoxin on oleic acid-induced lung injury.
Small-dose endotoxin (Etx) prevents pulmonary perfusion redistribution away from edematous dorsal lung regions after oleic acid (OA)-induced injury in dogs, causing a significant deterioration in oxygenation. We hypothesized that small-dose Etx might mediate this effect via polymorphonuclear neutrophil (PMN) priming with release of inflammatory mediators such as platelet activating factor (PAF) or secretory phospholipase A(2) (sPLA(2)). To test this hypothesis, we administered specific inhibitors directed against each mediator and used two strategies to generate neutropenia. PAF and sPLA(2) inhibitors were administered before OA injury, followed 2 h later by small-dose Etx (n = 4 each group). PMN depletion was achieved by hydroxyurea administration for 5 days before the study to achieve absolute neutrophil counts <1000/mm(3) (n = 4). Inhibition of PMN adherence to lung endothelium was achieved by the administration of an anti-CD18 monoclonal antibody immediately before lung injury (n = 5). Positron emission tomography was used to evaluate pulmonary perfusion distribution and lung water content. We observed no effect of these interventions on the perfusion pattern after Etx + OA. Thus, neither neutrophils nor PAF or sPLA(2) mediate the effects of Etx on the pattern of perfusion in this model of lung injury.


CONCLUSIONS
Acute respiratory failure is characterized by severe decreases in blood oxygen. The pattern of blood flow within the lungs can contribute to this problem. This study investigated the potential role of white blood cells and their products in mediating abnormal pulmonary blood flow patterns in an experimental animal model of respiratory failure.
Hill
Laureen L
LL
Departments of *Anesthesia, †Radiology, and ‡Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
Chen
Delphine L
DL
Kozlowski
James
J
Schuster
Daniel P
DP
D000818:Animals; D001834:Body Water / Q000187:drug effects / Q000502:physiology; D018821:CD18 Antigens / Q000276:immunology; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004731:Endotoxins / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology*; D019301:Oleic Acid / Q000633:toxicity*; D010101:Oxygen Consumption / Q000187:drug effects; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology; D010972:Platelet Activating Factor / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D014055:Tomography, Emission-Computed
D018821:CD18 Antigens; D004731:Endotoxins; D004791:Enzyme Inhibitors; D007211:Indoles; C095553:LY 311727; D010972:Platelet Activating Factor; D019301:Oleic Acid; D010741:Phospholipases A