AUGMENTATION OF ENDOTOXIN-INDUCED PULMONARY RESPONSES BY MONONUCLEAR CELL PHAGOCYTOSIS IN THE RETICULOENDOTHELIAL SYSTEM

Objective: To test the hypothesis that the effects of intravenous inje ction of latex particles would demonstrate the contribution of phagocy tosis by mononuclear phagocytes to the development of Escherichia coli -induced acute lung injury in neutropenic guinea pigs. Design: prospec tive, 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. In terventions: 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. coil endotoxin; a latex group (n = 7) recei ving 2 x 10(9)/kg of intravenous polystyrene latex (mean diameter 3.19 mu m); an endotoxin + rater group (n = 8); and an E. coil group (n = 7) receiving 2 x 10(9) live E. coli/kg. Measurements and Main Results: The lung wet/dry ratio was increased in the live E. coil-treated guin ea pigs (6.71 +/- 0.16 [SEM], p < .01) as compared with the saline con trol (5.40 +/- 0.16), whereas the ratio was not increased in the endot oxin (5.52 +/- 0.14) or latex (5.58 +/- 0.20) groups. However, the lun g wet/dry ratio was greater in the endotoxin + latex group (6.11 +/- 0 .16, p < .05) than in the saline control. The I-125 albumin lung tissu e/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 endot oxin group (0.22 +/- 0.10) and the latex (0.34 +/- 0.13) group. More t han 40% of the injected radiolabeled latex was observed to have? accum ulated in the reticuloendothelial system (liver and spleen), in both t he 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 th e saline control and the endotoxin groups, respectively. The percent d eposition of radiolabeled latex in the liver was greater in the endota xin group (51.7 + 3.8%, p < .05) than in the saline group (37.6 +/- 5. 9%). Conclusions: These findings suggest that, in neutropenic guinea p igs: a) the combination od endotoxin and latex particles induces acute lung injury; and bf the phagocytic properties of mononuclear phagocyt es in the reticuloendothelial system augment endotoxin-induced pulmona ry responses and may play a role in the development of live E. coli-in duced acute lung injury.