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Journal of Histochemistry and Cytochemistry, Vol. 51, 1307-1315, October 2003, Copyright © 2003, The Histochemical Society, Inc.

ARTICLE

Expression of the Integrin Subunit {alpha}8 in Murine Lung Development

Teresa E. Wagnera, Charles W. Freverta, Erica L. Herzogb, and Lynn M. Schnappa
a University of Washington, Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, Seattle, Washington
b Yale University, Division of Pulmonary and Critical Care Medicine, New Haven, Connecticut

Correspondence to: Teresa E. Wagner, 325 Ninth Ave., Box 359640, Seattle, WA 98104. E-mail: twagner@u.washington.edu

The complex interplay between cells and extracellular matrix (ECM) proteins is critical for lung development. Integrins are key modulators of this interaction. The integrin subunit {alpha}8 associates with the ß1-subunit to form an RGD-binding integrin. We previously showed that, in adult lung, {alpha}8 is expressed in contractile interstitial cells and smooth muscle cells and is upregulated in lung injury. To gain insight into the function of {alpha}8 during lung development, we examined the spatiotemporal expression of {alpha}8 throughout murine lung development. We compared the distribution of {alpha}8 with {alpha}-smooth muscle actin ({alpha}SMA), fibronectin ({alpha}8 ligand), and cytokeratin. {alpha}8 co-localized with {alpha}SMA and fibronectin in the peribronchial and perivascular regions. In all stages, {alpha}8 immunoreactivity was detected diffusely in the mesenchyme except for cells surrounding distal, newly forming airways. {alpha}8, {alpha}SMA, and fibronectin co-localized at tips of secondary septae in the alveolar stage. We conclude that {alpha}8 is marker for lung mesenchymal cells starting early in development. {alpha}8 is also a marker for smooth muscle cells, expressed as early as {alpha}SMA. Co-localization of {alpha}8 with fibronectin suggests a role in branching morphogenesis. Furthermore, {alpha}8 may participate in secondary septation by modulating signals from the extracellular matrix to alveolar myofibroblasts. (J Histochem Cytochem 1307–1315, 2003)

Key Words: lung, development, organogenesis, integrin, {alpha}8ß1


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