Saxena Rajiv K, Saxena Queen B, Weissman David N, Simpson Janet P, Bledsoe Toni A, Lewis Daniel M
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Toxicol Sci. 2003 May;73(1):66-71. doi: 10.1093/toxsci/kfg048. Epub 2003 Apr 15.
The effect of exposure to diesel exhaust particulate (DEP) on bacillus Calmette-Guerin (BCG) lung infection in mice was studied. C57Bl/6J female mice were infected with BCG (2.5 x 104 bacteria/mouse) by intrapulmonary instillation, with or without coadministration of DEP (100 microg/mouse). Five weeks later, mice exposed to DEP + BCG had about a four-fold higher BCG load in the lungs than mice exposed only to BCG (p < 0.05). DEP treatment alone had no effect on the total number of lung lymphocytes or numbers of T, B, or NK cells recovered from lungs. In contrast, BCG infection significantly increased (p< 0.05) recovery levels of all types of lymphocytes from lungs. Coexposure to DEP + BCG further increased the recovery of lymphocytes from lungs of BCG-infected mice. The pulmonary lymphocyte subpopulation expressing the greatest levels of mRNA for IFNgamma after BCG infection was CD4+ T cells. Expression levels were similar in mice exposed to BCG or BCG + DEP and were elevated as compared to noninfected mice and mice treated with DEP alone. Recovery of IFNgamma-secreting lymphocytes and IFNgamma-secreting T cells was significantly higher (p < 0.05) from lungs of BCG-infected mice as compared to control or DEP-exposed mice. BCG and BCG + DEP groups of mice did not differ significantly in the numbers of IFNgamma-secreting lymphocytes in lungs. Taken together, these results indicated that coexposure to DEP + BCG did not significantly affect the level of IFNgamma response of mice to BCG infection. However, DEP treatment was found to inhibit IFNgamma-induced nitric oxide (NO) production by mouse alveolar macrophages in vitro. Our results indicate that DEP exposure did not alter the IFNgamma response to BCG infection, but reduced responsiveness of alveolar macrophages to IFNgamma. Reduced sensitivity of DEP-exposed alveolar macrophages to IFNgamma may contribute to a greater load of BCG in the lungs of BCG-infected mice given DEP.
研究了暴露于柴油废气颗粒（DEP）对小鼠卡介苗（BCG）肺部感染的影响。通过肺内滴注法，将C57Bl/6J雌性小鼠感染卡介苗（2.5×10⁴个细菌/只小鼠），同时给予或不给予DEP（100微克/只小鼠）。五周后，暴露于DEP + BCG的小鼠肺部的卡介苗负荷比仅暴露于BCG的小鼠高约四倍（p < 0.05）。单独的DEP处理对肺淋巴细胞总数或从肺中回收的T、B或NK细胞数量没有影响。相比之下，BCG感染显著增加了（p<0.05）从肺中回收的所有类型淋巴细胞的水平。同时暴露于DEP + BCG进一步增加了BCG感染小鼠肺中淋巴细胞的回收。BCG感染后，表达IFNγ mRNA水平最高的肺淋巴细胞亚群是CD4⁺ T细胞。在暴露于BCG或BCG + DEP的小鼠中，表达水平相似，并且与未感染小鼠和仅用DEP处理的小鼠相比有所升高。与对照或DEP暴露小鼠相比，BCG感染小鼠肺中分泌IFNγ的淋巴细胞和分泌IFNγ的T细胞的回收率显著更高（p < 0.05）。BCG组和BCG + DEP组小鼠肺中分泌IFNγ的淋巴细胞数量没有显著差异。综上所述，这些结果表明，同时暴露于DEP + BCG对小鼠对BCG感染的IFNγ反应水平没有显著影响。然而，发现DEP处理在体外抑制小鼠肺泡巨噬细胞由IFNγ诱导的一氧化氮（NO）产生。我们的结果表明，暴露于DEP不会改变对BCG感染的IFNγ反应，但会降低肺泡巨噬细胞对IFNγ的反应性。暴露于DEP的肺泡巨噬细胞对IFNγ的敏感性降低可能导致给予DEP的BCG感染小鼠肺中BCG负荷增加。
