title: Attenuation by intravenous 2-chloroadenosine of acute lung injury induced by live escherichia coli or latex particles added to endotoxin in the neutropenic state.
abstract: 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.
authors.affiliation: Department of Medicine, Cardiopulmonary Division, School of Medicine, Keio University, Japan. sakamaki@tachikawa-hosp.gr.jp
authors.forename: Fumio
authors.initials: F
authors.lastname: Sakamaki
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Urano
authors.forename: Koichi
authors.initials: K
authors.lastname: Sayama
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Terashima
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Waki
authors.forename: Kenzo
authors.initials: K
authors.lastname: Soejima
authors.forename: Sadatomo
authors.initials: S
authors.lastname: Tasaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawafuji
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Minoru
authors.initials: M
authors.lastname: Kanazawa
mesh_terms: 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
chemical_list: D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D015762:2-Chloroadenosine; C044101:endotoxin, Escherichia coli