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PLoS One. 2013 Apr 25;8(4):e62045. doi: 10.1371/journal.pone.0062045. Print 2013.

Cavin1; a regulator of lung function and macrophage phenotype.

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1
The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, United States of America.

Abstract

Caveolae are cell membrane invaginations that are highly abundant in adipose tissue, endothelial cells and the lung. The formation of caveolae is dependent on the expression of various structural proteins that serve as scaffolding for these membrane invaginations. Cavin1 is a newly identified structural protein whose deficiency in mice leads to loss of caveolae formation and to development of a lipodystrophic phenotype. In this study, we sought to investigate the functional role of Cavin1 in the lung. Cavin1 deficient mice possessed dramatically altered distal lung morphology and exhibited significant physiological alterations, notably, increased lung elastance. The changes in distal lung architecture were associated with hypercellularity and the accumulation of lung macrophages. The increases in lung macrophages occurred without changes to circulating numbers of mononuclear cells and without evidence for increased proliferation. However, the increases in lung macrophages were associated with higher levels of macrophage chemotactic factors CXCL2 and CCL2 in BAL fluid from Cavin1-/- mice suggesting a possible mechanism by which these cells accumulate. In addition, lung macrophages from Cavin1-/- mice were larger and displayed measurable differences in gene expression when compared to macrophages from wild-type mice. Interestingly, macrophages were also increased in adipose tissue but not in liver, kidney or skeletal muscle from Cavin1-/- mice, and similar tissue specificity for macrophage accumulation was observed in lungs and adipose tissue from Caveolin1-/- mice. In conclusion, this study demonstrates an important role for Cavin1 in lung homeostasis and suggests that caveolae structural proteins are necessary for regulating macrophage number and phenotype in the lung.

PMID:
23634221
PMCID:
PMC3636273
DOI:
10.1371/journal.pone.0062045
[Indexed for MEDLINE]
Free PMC Article
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