title: Pulmonary macrophage antimicrobial activity in canine endotoxin shock and lung injury.
abstract: Bacterial sepsis and pneumonia are common complications of lung injury and predispose the host to a poor resolution. We studied the functional integrity of pulmonary macrophages derived from minced lung preparations in a canine model of endotoxin-induced shock with acute lung injury. Dogs given 2 mg/kg of Escherichia coli endotoxin 055:B5 developed classic shock symptoms with concomitant acute lung injury; control animals given saline showed no physiological or pathological abnormalities. Compared to previous work with this canine model, the lung injury in this extended time period (6 h) had progressed to include alveolar edema. Six hours after endotoxin infusion, the left lung was lavaged, perfused, and the resulting lung minced for isolation of pulmonary macrophages. The endotoxic-model pulmonary macrophages showed several significant functional differences from controls. Although they elicited greater production of H2O2 (p less than 0.05), both phagocytosis of radiolabeled Staphylococcus aureus and E. coli (p less than 0.05) and bactericidal activity (p less than 0.05) were diminished compared to controls. Compared to alterations previously described in alveolar macrophages, these cells produced less H2O2 and demonstrated abnormal bacterial killing at all time points. These observations suggest that the functional alterations of pulmonary macrophages that follow acute lung injury contribute to the ineffective cell-mediated antimicrobial response. These derangements may promote an increased risk of nosocomial pneumonia, the high mortality often observed subsequent to pneumonia, or the propagation of acute lung injury that facilitates respiratory failure.
authors: University of Arkansas for Medical Sciences, Little Rock.
authors: R F
authors: RF
authors: Jacobs
authors: D R
authors: DR
authors: Dorsey
authors: A F
authors: AF
authors: Tryka
authors: D R
authors: DR
authors: Tabor
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000209:etiology; D004285:Dogs; D006861:Hydrogen Peroxide / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000473:pathology; D055370:Lung Injury; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology; D012128:Respiratory Distress Syndrome / Q000209:etiology; D012772:Shock, Septic / Q000150:complications / Q000276:immunology* / Q000473:pathology
chemical_list: D006861:Hydrogen Peroxide