role of endogenous hiatamine on the pathogenesis of acute lung injury

Abstract

Role of endogenous histamine on the pathogenesis of endotoxin-induced acute lung injury Younsuck Koh, Tae-Hyung Kim, Chae-Man Lim, Mi Jung Kim, Tae Sun Shim, Sang Do Lee, Woo Sung Kim, Dong-Soon Kim, and Won Dong Kim. Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea Introduction : Histamine is widely distributed in the lung. It increases in capillary permeability and the P-selectin expression on the vascular endothelial cell surfaces. We studied the role of endogenous histamine on the pathogenesis of endotoxin-induced acute lung injury (ALI) in rats. Methods : We instilled either normal saline (control group) or lipopolysaccharide (3mg/Kg, LPS group) to tracheas of Sprague-Dawley rats. H1-receptor blocker (mepyramine, 10mg/Kg, H1RB group), H2-receptor blocker (ranitidine, 10mg/Kg, H2RB group), and H3-receptor blocker (thioperamide, 2mg/Kg, H3RB group) were administered through vein or peritoneum along with intratracheal LPS administration. Statistical significance was accepted at p < 0.05. Results : Compared to control group, histamine level in bronchoalveolar lavage (BAL) fluid was significantly higher at 2 h after LPS instillation in LPS group. Protein concentration, PMN cell count in BAL fluid, and myeloperoxidase (MPO) activity in the lung tissues were significantly higher at 6 h after LPS instillation in LPS group. Serum histamine level was significantly higher at 2 h in H1RB-group, and significantly lower at 1 h in H3RB-group compared to LPS group. Protein concentration in BAL fluid showed no significant differences between the LPS treated groups with/without antihistamine co-treatment. However, PMN cell count in BAL fluid and MPO activity in lung tissue were significantly lower in H2RB-group compared to LPS-group. Conclusions : Endogenous histamine might be involved in the recruitment of PMNs in LPS-induced ALI via H2 receptor. However, its role in ALI would not be significant in this model.