Augmentation of endotoxin-induced pulmonary responses by mononuclear cell phagocytosis in the reticuloendothelial system

Objective: To test the hypothesis that the effects of intravenous injection of latex particles would demonstrate the contribution of phagocytosis by mononuclear phagocytes to the development of Escherichia coli-induced acute lung injury in neutropenic guinea pigs. Design: Prospective, controlled, experimental study. Intravenously injected the latex particles into 41 guinea pigs to investigate the contribution of the phagocytosis in acute lung injury. Subjects: Forty-one guinea pigs. Interventions: Forty-one guinea pigs were divided into five experimental groups: a saline group (n = 9); an endotoxin group (n = 10) receiving 2 mg/kg of intravenous E. coli endotoxin; a latex group (n = 7) receiving 2 x 10⁹/kg of intravenous polystyrene latex (mean diameter 3.19 μm); an endotoxin + latex group (n = 8); and an E. coli group (n = 7) receiving 2 x 10⁹ live E. coli/kg. Measurements and Main Results: The lung wet/dry ratio was increased in the live E. coli-treated guinea pigs (6.71±0.16 [SEM], p < .01) as compared with the saline control (5.40±0.16), whereas the ratio was not increased in the endotoxin (5.52±0.14) or latex (5.58±0.20) groups. However, the lung wet/dry ratio was greater in the endotoxin + latex group (6.11±0.16, p < .05) than in the saline control. The ¹²⁵I albumin lung tissue/plasma ratio was greater in the E. coli (2.00±0.29, p < .01) and endotoxin + latex (0.84±0.12, p < .05) groups than in the saline group (0.18±0.07), whereas no increases were observed in the endotoxin group (0.22±0.10) and the latex (0.34±0.13) group. More than 40% of the injected radiolabeled latex was observed to have accumulated in the reticuloendothelial system (liver and spleen), in both the saline control (40.1 ±2.3%, n = 4) and endotoxin (57.3±6.8%, n = 5) groups, with 2.6± 1.5% and 3.1±1.7% in the lungs for the saline control and the endotoxin groups, respectively. The percent deposition of radiolabeled latex in the liver was greater in the endotoxin group (51.7± 3.8%, p < .05) than in the saline group (37.6±5.9%). Conclusions: These findings suggest that, in neutropenic guinea pigs: a) the combination of endotoxin and latex particles induces acute lung injury; and b) the phagocytic properties of mononuclear phagocytes in the reticuloendothelial system augment endotoxin-induced pulmonary responses and may play a role in the development of live E. coli-induced acute lung injury.