Distribution of Integrins During Human Fetal Lung Development

Abstract

SUMMARYInteractions between epithelial cells and the extracellular matrix through integrins play a key role in the development of the lung by modulating branching morphogenesis, epithelial cell polarization, and differentiation. To determine the role of integrins during the different stages of lung development, we investigated the distribution of eight integrin subunits in the trachea and lung from human fetuses. In distal airways, during the early pseudoglandular stage of development, the ␣2-, ␣5-, ␣6-, ␣v-, and ␤1-subunits were detected in all epithelial cell plasma membranes, and polarized but undifferentiated tracheal epithelial cells expressed ␣3-, ␣6-, and ␤1-subunits in the plasma membrane of the cells facing the basement membrane. The ␣6-and ␤4-chains were detected along the basal plasma membrane of the basal cells in differentiated tracheal epithelia. The ␣4-subunit was detected in all respiratory cells throughout fetal development. In the submucosal glands, myoepithelial cells expressed the integrin subunits found in the undifferentiated cells of the developing airways, whereas the secretory cells expressed only ␣2-, ␣3-, ␣4-, ␣6-, and ␤1-subunits. These results demonstrate differential expression of integrins during lung development and suggest that integrins may play multiple roles in organogenesis and maturation of respiratory surface epithelium and glands. (J Histochem Cytochem 46:803-810, 1998)

Integrin characterization in pulmonary bronchioles

“…Each integrin is a heterodimer that contains an a and a h subunit with each subunit having a large extracellular domain, a single membrane spanning region, and in most cases (other than h 4 ), a short cytoplasmic domain (Frisch and Ruoslahti, 1997;Hynes, 1992Hynes, , 2000. The integrin receptor family of vertebrates includes at least 16 distinct a subunits and at least 8 h subunits which can associate to form more than 20 distinct integrins (Coraux et al, 1998;Frisch and Ruoslahti, 1997;Hynes, 1992;Ingber, 1991;Liapis and Hutton, 1997;Mizejewski, 1999;Schwartz, 1997).…”

“…In addition, during dynamic and complex processes, such as organ development and tumor progression and metastasis, the cellular distribution and/or intensity of expression may change (Arroyo et al, 2000;Boudreau and Jones, 1999;Brown, 2000;Coraux et al, 1998;Dedhar and Hannigan, 1996;Felding-Habermann et al, 2001;Frisch and Ruoslahti, 1997;Giancotti, 1997;Hemler, 1998;Howe et al, 1998;Hynes, 1992;Ingber, 1991;Legier et al, 2001;Schwartz, 1997;Shyy and Chien, 1997).…”

Aberrant cell adhesion molecule expression in human bronchopulmonary sequestration and congenital cystic adenomatoid malformation

“…␣ 2 ␤ 1 -integrin receptors are thought to promote mesenchymal-epithelial cell contacts as epithelial cells migrate into surrounding mesenchyme and associate with extracellular matrix binding partners and other cells (16,67). In CCAM tissue, the increased intensity of ␣ 2 -integrin localization with antibody 2 compared with lung tissue adjacent to CCAM cysts suggests that part of the intensity of ␣ 2 -integrin immunostaining in the CCAM cysts was due to the 130-kDa ␣ 2 -isoform detected with Western blotting.…”

“…␤ 1 -integrin is the major partner for ␣ 2 -and ␣ 3 -integrin in lung with formation of activated ␣ 2 ␤ 1 -or ␣ 3 ␤ 1 -integrin receptors leading to changes in inside-out and outside-in integrin signaling partly through recruitment of signaling molecules to sites in the cytoplasmic tail of ␤ 1 -integrin (16,17,53). Although we detected differential changes in ␣ 2 -and ␣ 3 -integrin in BPS and CCAM, no differences in ␤ 1 -integrin were detected between canalicular and alveolar stage normal human lung tissue and BPS and CCAM tissue samples (Fig.…”

“…Integrins are located both in lung mesodermal and epithelial cells where distinct temporal, cellular, and regional expression domains of different integrins are poised to influence airway branching and lung cell fate. Several integrins have distinct patterns of expression during lung development suggesting unique roles for different integrin receptor complexes at different times in development and in different regions within the developing lung (16,67). ␤ 1 -integrin is the preferred partner for ␣ 2 -and ␣ 3 -integrin in lung with specificity being determined by different cell types in which the integrins are expressed (33).…”