Qureshi Mahboob H, Cook-Mills Joan, Doherty Dennis E, Garvy Beth A
Department of Microbiology, University of Kentucky, Veterans Administration Medical Center, Lexington, KY 40536, USA.
J Immunol. 2003 Nov 1;171(9):4700-7. doi: 10.4049/jimmunol.171.9.4700.
Neonatal mice have a delayed CD4-mediated inflammatory response to Pneumocystis carinii (PC) infection in the lungs that corresponds to a delayed TNF-alpha response and a delayed clearance of the organisms compared with adult mice. Since TNF-alpha is known to drive the up-regulation of adhesion molecules, we examined the expression and function of adhesion molecules in the lungs of neonatal mice. The expression of both ICAM-1 and VCAM-1 was significantly lower in the lungs of PC-infected neonatal mice compared with adults. Additionally, migration of neonatal T cells across endothelial cells expressing VCAM-1 and monocyte chemotactic protein-1 was aberrant compared with that in adult T cells, although alpha(4)beta(1) integrin-mediated adhesion of neonatal lymphocytes was comparable to that of adult lymphocytes. Treatment of neonatal mice with exogenous TNF-alpha resulted in increased expression of ICAM-1 and VCAM-1 as well as increased expression of chemokines, resulting in infiltration of CD4(+) cells into the lungs. Treatment with exogenous TNF-alpha resulted in a trend (although not statistically significant) toward a reduction of PC organisms from the lungs. These data indicate that neonatal lung endothelial cells do not up-regulate ICAM-1 and VCAM-1 in response to PC infection, probably due to depressed TNF-alpha production. Additionally, neonatal T cells are defective in the ability to migrate across endothelial cells.
与成年小鼠相比，新生小鼠对肺部卡氏肺孢子虫（PC）感染的CD4介导的炎症反应延迟，这与TNF-α反应延迟和病原体清除延迟相对应。由于已知TNF-α可驱动黏附分子的上调，我们研究了新生小鼠肺中黏附分子的表达和功能。与成年小鼠相比，PC感染的新生小鼠肺中ICAM-1和VCAM-1的表达均显著降低。此外，与成年T细胞相比，新生T细胞跨表达VCAM-1和单核细胞趋化蛋白-1的内皮细胞的迁移异常，尽管α(4)β(1)整合素介导的新生淋巴细胞黏附与成年淋巴细胞相当。用外源性TNF-α处理新生小鼠导致ICAM-1和VCAM-1表达增加以及趋化因子表达增加，导致CD4(+)细胞浸润到肺中。用外源性TNF-α处理导致肺中PC病原体有减少的趋势（尽管无统计学意义）。这些数据表明，新生肺内皮细胞不会因PC感染而上调ICAM-1和VCAM-1，这可能是由于TNF-α产生受抑。此外，新生T细胞跨内皮细胞迁移的能力存在缺陷。
