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Published ahead of print on June 26, 2003, doi:10.1165/rcmb.2002-0227OC

Am. J. Respir. Cell Mol. Biol., Volume 29, Number 6, December 2003, 661-668

A more recent version of this article appeared on December 1, 2003
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Submitted on November 1, 2002
Revised on June 26, 2003

CXC chemokines and their receptor are expressed in Type II Cells and upregulated by injury

Jeff N Vanderbilt1, Edward M Mager1, Lennell Allen1, Teiji Sawa1, Jeanine Wiener-Kronish1, Robert F Gonzalez1, and Leland G Dobbs1*

1 CVRI,Med,Peds,Anesthesia, University of California San Francisco, San Francisco, CA, USA

* To whom correspondence should be addressed. E-mail: dobbs{at}itsa.ucsf.edu.

The proinflammatory CXC chemokines GRO, CINC-2{alpha} and 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 P.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-2{alpha} 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-2{alpha} 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 immunological 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.




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