Vanderbilt Jeff N, Mager Edward M, Allen Lennell, Sawa Teiji, Wiener-Kronish Jeanine, Gonzalez Robert, Dobbs Leland G
Cardiovascular Research Institute/Pediatrics, University of California San Francisco, Laurel Heights Campus, Suite 150, 3333 California Street, San Francisco, CA 94118, USA.
Am J Respir Cell Mol Biol. 2003 Dec;29(6):661-8. doi: 10.1165/rcmb.2002-0227OC. Epub 2003 Jun 26.
The proinflammatory CXC chemokines GRO, CINC-2alpha, and macrophage inflammatory protein (MIP)-2 are a closely related family of neutrophil chemoattractants. Here, we report that freshly isolated alveolar Type II (TII) cells express these chemokine mRNAs at much higher levels than do freshly isolated Type I cells or alveolar macrophages (AM). TII cells also express CXCR2, the receptor for these chemokines. Lung injury caused by acid or Pseudomonas aeruginosa (Pa) caused an increase in TII cell expression of chemokine mRNAs and GRO protein. We compared the time courses of chemokine mRNA expression in cultured TII cells and AM. In TII cells, GRO mRNA levels were stable over 4 h, but decreased to undetectable levels by 24 h. CINC-2alpha and MIP-2 mRNA levels were low in freshly isolated cells, increased over 2-4 h in culture, and by 24 h dropped to undetectable levels. In contrast, none of these chemokine mRNAs were detected in freshly isolated AM, but expression was induced by tissue culture. In summary, we have shown that TII alveolar epithelial cells produce three of the major proinflammatory CXC chemokines (GRO, CINC-2alpha, and MIP-2) and their cognate receptor CXCR2. Chemokine expression is upregulated in response to lung injury. These observations support a central role for the TII cell as an immunologic effector cell in the alveolus and raise intriguing questions about how CXC chemokines and receptors modulate diverse normal and pathologic cellular responses in the alveoli.
促炎CXC趋化因子GRO、CINC-2α和巨噬细胞炎性蛋白（MIP）-2是密切相关的中性粒细胞趋化因子家族。在此，我们报告，新鲜分离的肺泡II型（TII）细胞表达这些趋化因子mRNA的水平比新鲜分离的I型细胞或肺泡巨噬细胞（AM）高得多。TII细胞还表达这些趋化因子的受体CXCR2。酸或铜绿假单胞菌（Pa）引起的肺损伤导致TII细胞趋化因子mRNA和GRO蛋白表达增加。我们比较了培养的TII细胞和AM中趋化因子mRNA表达的时间进程。在TII细胞中，GRO mRNA水平在4小时内稳定，但在24小时时降至无法检测的水平。CINC-2α和MIP-2 mRNA水平在新鲜分离的细胞中较低，在培养2-4小时内升高，到24小时时降至无法检测的水平。相比之下，新鲜分离的AM中未检测到这些趋化因子mRNA中的任何一种，但组织培养可诱导其表达。总之，我们已经表明，TII肺泡上皮细胞产生三种主要的促炎CXC趋化因子（GRO、CINC-2α和MIP-2）及其同源受体CXCR2。趋化因子表达在肺损伤时上调。这些观察结果支持TII细胞作为肺泡中免疫效应细胞的核心作用，并引发了关于CXC趋化因子和受体如何调节肺泡中各种正常和病理细胞反应的有趣问题。
