Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012:729:157-79.
doi: 10.1007/978-1-4614-1222-9_11.

Caveolins and lung function

Affiliations
Review

Caveolins and lung function

Nikolaos A Maniatis et al. Adv Exp Med Biol. 2012.

Abstract

The primary function of the mammalian lung is to facilitate diffusion of oxygen to venous blood and to ventilate carbon dioxide produced by catabolic reactions within cells. However, it is also responsible for a variety of other important functions, including host defense and production of vasoactive agents to regulate not only systemic blood pressure, but also water, electrolyte and acid-base balance. Caveolin-1 is highly expressed in the majority of cell types in the lung, including epithelial, endothelial, smooth muscle, connective tissue cells, and alveolar macrophages. Deletion of caveolin-1 in these cells results in major functional aberrations, suggesting that caveolin-1 may be crucial to lung homeostasis and development. Furthermore, generation of mutant mice that under-express caveolin-1 results in severe functional distortion with phenotypes covering practically the entire spectrum of known lung diseases, including pulmonary hypertension, fibrosis, increased endothelial permeability, and immune defects. In this Chapter, we outline the current state of knowledge regarding caveolin-1-dependent regulation of pulmonary cell functions and discuss recent research findings on the role of caveolin-1 in various pulmonary disease states, including obstructive and fibrotic pulmonary vascular and inflammatory diseases.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Expression of caveolin-1 in pulmonary epithelium and endothelium during mouse lung development. Caveolin-1 and -2 expression begins at day E10 in pulmonary endothelial cells and E19 in alveolar epithelial cells. The temporal and cell-specific regulation of caveolin expression in the lung may play an important role in the mechanisms which govern branching morphogenesis and alveolar maturation during lung development.
Figure 2
Figure 2
Architectural changes of vascular and alveolar compartments in Cav1−/− lungs. Vascular and alveolar casts were generated by chilling lungs after perfusion of fluorescent beads in a solution containing 0.3% agarose via pulmonary cannula and trachea, respectively. 3D rendering of thick lung section confocal z-stack images shows nonhomogeneous filling of capillaries and enlarged airspaces in Cav1−/− compared to wild type (WT) lungs. Reproduced with permission from Maniatis NA, Am J Physiol 2008; 294(5):L865–873. © 2008, the American Physiological Society. A color version of this image is available online at www.landesbioscience.com/curie.
Figure 3
Figure 3
Ultrastructure of alveolar septa in wild type and Cav1−/− lungs. Note absence of caveolae, hypercellularity and septal thickening of Cav1−/− lung (top right) and abundance of caveolae in thin alveolar, and capillary gas exchange cellular membranes of WT mouse lung (top left and bottom). Images courtesy of Oleg Chaga, PhD., University of Illinois-Chicago.
Figure 4
Figure 4
Modulation of Toll-like-receptor-dependent signaling pathways by caveolin-1. Data obtained primarily on macrophages (left panel) favor a suppressive function of caveolin-1 on Toll-like receptor-4 (TLR-4) signaling. This is accomplished on several levels, starting by physical association with the receptor within caveolae, which presumably diminishes binding to adaptor protein MyD88, a required step for propagation of the TLR-4 signal upon docking of lipopolysaccharide (LPS). Activation of heme oxygenase-derived CO production by p38, which is expected to occur following TLR-4 ligation by LPS, is an additional mechanism to turn off the TLR-4 signal (adapted from Wang et al 2009). A seemingly opposing function of caveolin-1 has been advocated in knockdown experiments in endothelial cells (right panel). Excessive free radical (nitric oxide-NO and superoxide-O2) production due to lack of caveolin-1-mediated endothelial NO synthase (eNOS) inhibition may lead to nitration of interleukin-1-associated receptor kinase (IRAK)-4, an important intermediate between TLR-4 and its effector molecules nuclear factor-κ (NF-κB) and mitogen-activated kinases (p38, ERK1/2, JNK). Hypothetically, this mechanism could take effect in situations in which eNOS is uncoupled from caveolin-1, as may occur in the presence of vasoactive mediators including thrombin. In this case, dual activation of eNOS due to Ca++ influx and dissociation from caveolin-1 could result in production of large amounts of free radicals and tyrosine nitration via the reactive metabolite peroxynitrite (ONOO). A color version of this image is available online at www.landesbioscience.com/curie.

Similar articles

Cited by

References

    1. West JB, Watson RR, Fu Z. The human lung: did evolution get it wrong? Eur Respir J. 2007;29(1):11–17. - PubMed
    1. West JB. Thoughts on the pulmonary blood-gas barrier. Am J Physiol Lung Cell Mol Physiol. 2003;285(3):L501–L513. - PubMed
    1. Gehr P, Bachofen M, Weibel ER. The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respir Physiol. 1978;32(2):121–140. - PubMed
    1. Phillips CG, Kaye SR. On the asymmetry of bifurcations in the bronchial tree. Respir Physiol. 1997;107(1):85–98. - PubMed
    1. Stevens T, Phan S, Frid MG, et al. Lung vascular cell heterogeneity: endothelium, smooth muscle, and fibroblasts. Proc Am Thorac Soc. 2008;5(7):783–791. - PMC - PubMed

LinkOut - more resources