The Importance of Polymorphonuclear Leukocytes in Lipopolysaccharide-Induced Superoxide Anion Production and Lung Injury: Ex Vivo Observation in Rat Lungs

Abstract

The purpose of this study is to determine if the polymorphonuclear leukocyte (PMN) is a major causative agent for lipopolysaccharide (LPS)-induced lung injury and responsible for the excess production of superoxide anion in the lung. We measured superoxide anion production from the lung and pulmonary capillary permeability in rats with and without PMN depletion. The superoxide anion production from the lung was measured using a purpose-built ex vivo chemiluminescence apparatus. Pulmonary capillary permeability was evaluated by the Evans blue dye extravasation method. PMN sequestration was determined by counting PMNs in histologic tissue specimens using microscopy. All rats received 3 mg/kg LPS intravenously. Examinations were undertaken at 2, 6, and 12 h after the LPS injection. The PMN-depleted group received cyclophosphamide 4 days before the LPS injection, which resulted in a PMN count of less than 200 cells/microliter. In rats without PMN depletion, Evans blue dye extravasation increased significantly at 12 h after the LPS injection; PMN sequestration increased at 2, 6, and 12 h after the LPS injection; and superoxide anion production increased at 6 h and remained elevated at 12 h after the LPS injection. The increased permeability, PMN sequestration, and superoxide anion production were not seen in the PMN-depleted group. The contribution of the xanthine/xanthine oxidase system and alveolar macrophages to the observed superoxide anion production was negligible. We conclude that, in rats, the PMN is a major causative agent in LPS-induced lung injury and is responsible for the excess production of superoxide anion in the lung.

Role of Pulmonary Alveolar Macrophages in Defense of the Lung againstPseudomonas aeruginosa

“…PMNs, but not AM, actively phagocytosed P. aeruginosa, as shown in BAL preparations from both groups of mice, indicating that PMNs actively participated in bacterial clearance. In the uninfected or untreated lung, PMNs comprise a small proportion of cells in the lower respiratory tract and macrophages constitute 85 to 98% of cells (15,26,29). However, the number of PMNs increases in lungs challenged with P. aeruginosa by intratracheal inoculation (19).…”

Production of oxidants in alveolar macrophages and blood leukocytes

“…The relative contributions of alveolar macrophages, monocytes and polymorphonuclear neutrophils to the overall respiratory burst in lung inflammatory disorders probably varies for each specific disease [4], as indicated in studies in patients with adult respiratory distress syndrome, sarcoidosis and idiopathic pulmonary fibrosis [5,6,32,37,39] as well as in animal studies, using experimental models of lung injury [40,41]. In conclusion, the present study clearly demonstrates that alveolar macrophages, monocytes and polymorphonuclear neutrophils posess significant differences in potential to increase their intracellular levels of oxidants upon stimulation.…”

Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms

“…Elaboration of TNF-α and IL-1 in LPS models of sepsis leads to neutrophil recruitment and inflammatory damage to both liver and lung tissue [29,30]. Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) mediate neutrophil infiltration [31].…”