Mechanisms of ozone-induced inhibitory effect of bronchoalveolar lavage fluid on alveolar macrophage-mediated immunosuppressive activity in rats.
Resident alveolar macrophages (AM) play an important immunomodulatory role via suppression of lymphocyte proliferation, and nitric oxide (NO) plays a crucial role in this immunosuppression of AM. Our previous report suggested that during ozone (O3)-induced lung inflammation, bronchoalveolar lavage fluid (BALF) inhibited AM-mediated immunosuppression and concanavalin A (Con A)-induced proliferation of lymph node cells (LNC) [E. Koike et al. (1998) Toxicol. Sci. 41, 217-223]. In these studies, we investigated the mechanisms of the inhibition of BALF from O3-exposed rats (O3-BALF). We investigated whether BALF might affect (1) the interferon-gamma (IFN-gamma) production by Con A-stimulated LNC and IFN-gamma-induced NO production by AM, and (2) the interleukin (IL)-2 production by Con A-stimulated LNC and IL-2-induced LNC proliferation. These results demonstrated that O3-BALF inhibited IFN-gamma production by Con A-stimulated LNC, IFN-gamma-induced NO production by AM, and IL-2-induced LNC proliferation. In addition, the major inhibitory factor against AM-mediated immunosuppression in O3-BALF may be a protein of greater than 10 kDa.
Koike
E
E
Department of Medical Sciences, University of Tsukuba, Japan.
Kobayashi
T
T
Murakami
M
M
McWilliam
A S
AS
Holt
P G
PG
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002455:Cell Division; D003208:Concanavalin A / Q000494:pharmacology; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D009500:Neutralization Tests; D009569:Nitric Oxide / Q000378:metabolism; D010126:Ozone / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar
D008934:Mitogens; D003208:Concanavalin A; D009569:Nitric Oxide; D010126:Ozone; D007371:Interferon-gamma