Attenuation by intravenous 2-chloroadenosine of acute lung injury induced by live escherichia coli or latex particles added to endotoxin in the neutropenic state.
Although neutrophil depletion can reduce the level of acute lung injury (ALI) induced by Escherichia coli endotoxin, that induced by live E coli cannot be attenuated even in neutropenia. This suggests that live E coli cause ALI by way of an mechanism independent of circulating neutrophil. Tumor necrosis factor-alpha (TNF-alpha), which is released from monocytes and macrophages, is a proinflammatory cytokine that is recognized as a central mediator of several forms of inflammation. In this controlled experimental study, we examined the effects of an adenosine-receptor agonist, 2-chloroadenosine (2CA), that has suppressive effects on various cell types and TNF-alpha, on endotoxin plus latex particles, and on ALI induced by live E coli in the neutropenic state. We studied 42 guinea pigs rendered neutropenic by means of intraperitoneal cyclophosphamide administration. Experimental groups consisted of (1) a saline-solution control group; (2) an endotoxin (0.2 mg/kg)-treated group; (3) a group treated with endotoxin plus 2CA (10 micro g/kg); (4) a group treated with latex (2 x 10(9)/kg); (5) a group exposed to endotoxin and latex; (6) a group exposed to endotoxin, latex, and 2CA; (7) a group exposed to E coli (2 x 10(9)/kg); and (8) a group exposed to E coli and 2CA. The injection of endotoxin alone in neutropenic animals did not increase the indexes of ALI (lung tissue/plasma ratio [T/P] and lung wet weight/dry weight ratio [W/D], calculated with the use of iodine 125-labeled albumin). In contrast, these indexes were increased in the endotoxin-and-latex groups compared with those of the control group. ALI in the endotoxin-and-latex group was attenuated by intravenous 2CA. The intravenous injection of live E coli also caused increases in T/P, W/D, and plasma TNF-alpha, but thse were limited by 2CA. In summary, ALI induced by latex particles added to endotoxin and live E coli in the neutropenic state was attenuated by 2CA, suggesting a partial contribution of various cell types or humoral mediators as a neutrophil-independent pathway in its pathogenesis.
Sakamaki
Fumio
F
Department of Medicine, Cardiopulmonary Division, School of Medicine, Keio University, Japan. sakamaki@tachikawa-hosp.gr.jp
Ishizaka
Akitoshi
A
Urano
Tetsuya
T
Sayama
Koichi
K
Nakamura
Hidetoshi
H
Terashima
Takeshi
T
Waki
Yasuhiro
Y
Soejima
Kenzo
K
Tasaka
Sadatomo
S
Sawafuji
Makoto
M
Kobayashi
Kouichi
K
Yamaguchi
Kazuhiro
K
Kanazawa
Minoru
M
D015762:2-Chloroadenosine / Q000494:pharmacology*; D000208:Acute Disease; D000818:Animals; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000276:immunology*; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008171:Lung Diseases / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D008863:Microspheres; D009503:Neutropenia / Q000276:immunology* / Q000382:microbiology; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D015762:2-Chloroadenosine; C044101:endotoxin, Escherichia coli