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.


METHODS
Prospective, controlled, experimental study. Intravenously injected the latex particles into 41 guinea pigs to investigate the contribution of the phagocytosis in acute lung injury.


METHODS
Forty-one guinea pigs.


METHODS
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 10(9)/kg of intravenous polystyrene latex (mean diameter 3.19 micrometers); an endotoxin + latex group (n=8); and an E. coli group (n=7) receiving 2 x 10(9) live E. coli/kg.


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.
Ishizaka
A
A
Department of Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Hasegawa
N
N
Sayama
K
K
Urano
T
T
Nakamura
H
H
Sakamaki
F
F
Soejima
K
K
Waki
Y
Y
Tasaka
S
S
Nakamura
M
M
Matsubara
H
H
Kanazawa
M
M
D000818:Animals; D004731:Endotoxins / Q000009:adverse effects*; D004926:Escherichia coli; D005260:Female; D006168:Guinea Pigs; D007275:Injections, Intravenous; D007840:Latex / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008171:Lung Diseases / Q000209:etiology / Q000382:microbiology / Q000503:physiopathology*; D012157:Mononuclear Phagocyte System / Q000187:drug effects* / Q000503:physiopathology; D009503:Neutropenia / Q000503:physiopathology; D010587:Phagocytosis / Q000187:drug effects*; D011446:Prospective Studies; D011897:Random Allocation
D004731:Endotoxins; D007840:Latex