Altered release of eicosanoids by rat alveolar macrophages during granulomatous pulmonary inflammation.
Release of arachidonic acid metabolites (eicosanoids) by alveolar macrophages may be important in regulating pulmonary inflammatory reactions. The purpose of this study was to characterize eicosanoids released by rat alveolar macrophages during the evolution of experimentally induced pulmonary inflammation. Immunization with subcutaneous bacillus Calmette-Guerin (BCG) followed 2 wk later by intravenous BCG challenge resulted in mild granulomatous pulmonary inflammation for up to 30 days. At serial intervals, alveolar macrophages were lavaged from the BCG-treated rats as well as from control normal rats. Lavaged macrophages were cultured in vitro, and culture supernatants were assayed by radioimmunoassay for release of prostaglandin E2 (PGE2), Leukotriene B4 (LTB4), and thromboxane B2 (TXB2). Cells were cultured alone, or with added LPS or calcium ionophore A23187 to stimulate eicosanoid release. During BCG-induced inflammation, spontaneous release of PGE2 and LTB4 was unchanged, while spontaneous release of TXB2 was depressed acutely and then returned to control levels. The capacity of alveolar macrophages to release specific eicosanoids in response to an in vitro stimulus was dramatically altered during the course of BCG-induced inflammation. Stimulated release of PGE2 was transiently increased during acute lung injury, but stimulated release of LTB4 was significantly decreased at all stages of inflammation. Stimulated release of TXB2 was unchanged. These results indicate that during the course of granulomatous pulmonary inflammation there are dynamic changes in the profile of eicosanoids released by alveolar macrophages, both spontaneously and in response to in vitro stimulation. This alteration in the release of eicosanoids by alveolar macrophages may be an important factor in the resolution of pulmonary inflammation.
Shellito
J
J
Department of Veteran Affairs Medical Center, San Francisco, California.
Sniezek
M
M
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D002478:Cells, Cultured; D003470:Culture Media; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D006099:Granuloma / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008171:Lung Diseases / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009163:Mycobacterium bovis; D011650:Pulmonary Alveoli; D011863:Radioimmunoassay; D051381:Rats; D011916:Rats, Inbred F344; D013929:Thromboxane B2 / Q000378:metabolism
D003470:Culture Media; D015777:Eicosanoids; D007975:Leukotriene B4; D013929:Thromboxane B2; D015232:Dinoprostone