CXC chemokines and their receptors are expressed in type II cells and upregulated following lung injury.
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.
Vanderbilt
Jeff N
JN
Cardiovascular Research Institute/Pediatrics, University of California San Francisco, Laurel Heights Campus, Suite 150, 3333 California Street, San Francisco, CA 94118, USA.
Mager
Edward M
EM
Allen
Lennell
L
Sawa
Teiji
T
Wiener-Kronish
Jeanine
J
Gonzalez
Robert
R
Dobbs
Leland G
LG
D000818:Animals; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D015846:Monokines / Q000235:genetics / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; C513296:Cxcl2 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D015846:Monokines; D012333:RNA, Messenger; D023063:Receptors, Interleukin-8B