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CXC Chemokines and Their Receptors Are Expressed in Type II Cells and Upregulated following Lung Injury

Cardiovascular Research Institute, and Departments of Medicine, Pediatrics, and Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California

Address correspondence to: Dr. Leland G. Dobbs, Cardiovascular Research Institute/Pediatrics, University of California San Francisco, Laurel Heights Campus, Suite 150, 3333 California Street, San Francisco, CA 94118. E-mail: dobbs{at}itsa.ucsf.edu

The proinflammatory CXC chemokines GRO, CINC-2, 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-2 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, 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.

Abbreviations: alveolar macrophages, AM • cytokine induced neutrophil chemoattractant, CINC • conserved glutamate-leucine-arginine sequence, ELR • growth related oncogene, GRO • interleukin, IL • macrophage inflammatory protein, MIP • Pseudomonas aeruginosa, Pa • surfactant protein, SP • alveolar type II cells, TII cells

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