Koike E, Kobayashi T, Murakami M, McWilliam A S, Holt P G
Department of Medical Sciences, University of Tsukuba, Japan.
J Leukoc Biol. 1999 Jul;66(1):75-82. doi: 10.1002/jlb.66.1.75.
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.
驻留肺泡巨噬细胞（AM）通过抑制淋巴细胞增殖发挥重要的免疫调节作用，而一氧化氮（NO）在AM的这种免疫抑制中起关键作用。我们之前的报告表明，在臭氧（O3）诱导的肺部炎症期间，支气管肺泡灌洗液（BALF）抑制了AM介导的免疫抑制以及伴刀豆球蛋白A（Con A）诱导的淋巴结细胞（LNC）增殖[E. Koike等人（1998年）《毒理学科学》41卷，217 - 223页]。在这些研究中，我们研究了来自O3暴露大鼠的BALF（O3 - BALF）的抑制机制。我们研究了BALF是否可能影响：（1）Con A刺激的LNC产生干扰素 - γ（IFN - γ）以及IFN - γ诱导的AM产生NO，以及（2）Con A刺激的LNC产生白细胞介素（IL） - 2以及IL - 2诱导的LNC增殖。这些结果表明，O3 - BALF抑制了Con A刺激的LNC产生IFN - γ、IFN - γ诱导的AM产生NO以及IL - 2诱导的LNC增殖。此外，O3 - BALF中对抗AM介导的免疫抑制的主要抑制因子可能是一种大于10 kDa的蛋白质。
