Abstract. The integrin av[36 is only expressed in epithelial cells. In healthy adult epithelia, this receptor is barely detectable, but expression is rapidly induced following epithelial injury. Mice homozygous for a null mutation in the gene encoding the 1~6 subunit had juvenile baldness associated with infiltration of macrophages into the skin, and accumulated activated lymphocytes around conducting airways in the lungs. 136 -/-mice also demonstrated airway hyperresponsiveness to acetylcholine, a hallmark feature of asthma. These resuits suggest that the epithelial integrin av136 participates in the modulation of epithelial inflammation. Genetic or acquired alterations in this integrin could thus contribute to the development of inflammatory diseases of epithelial organs, such as the lungs and skin.
INTEGRINS are heterodimeric receptors for extracetlular matrix and cell surface ligands that have been suggested to play important roles in development, inflammation, wound healing, and tumorigenesis (Hynes, 1987(Hynes, , 1992Ruoslahti and Pierschbacher, 1987). In vitro, integrins have been shown to contribute to cell adhesion, spreading and migration, and to more complex processes including cell proliferation, apoptosis, and the regulation of gene expression (Hynes, 1992;Juliano and Haskill, 1993). In vivo, the biological importance of integrins has been most clearly demonstrated for control of leukocyte migration and platelet aggregation. At least some integrins play critical roles in development, as demonstrated by the findings that the inactivation of the genes encoding two different integrin ~ subunits, a4 (Yang et al., 1995) and ~5 (Yang et al., 1993), are embryonic lethal mutations. However, although epithelial cells express several different integrins, the roles epithelial integrins play in health and disease remain largely unknown.The integrin [36 subunit is expressed exclusively in epithelial cells, and only in a single integrin heterodimer, av[36, a receptor for the extracellular matrix proteins fibronectin (Busk et al., 1992;Weinacker et al., 1994) and tenascin (Prieto et al., 1993). av[36 is highly expressed in the lung, skin, and kidney during organogenesis (Breuss et al., 1995). In epithelia of healthy adults, this receptor is expressed at very low levels, except in the endometrium, where av[36 is highly expressed during the secretory phase of the menstrual cycle, and in the lung and kidney, where cw136 is often expressed in a patchy distribution associated with subclinical inflammation (Breuss et al., 1995). av[36 is highly expressed in response to injury or inflammation, and in malignant epithelial neoplasms (Breuss et al., 1995). For example, in experimental skin wounds, av136 is highly expressed in the keratinocytes at the wound edge within a few days of wounding, where it remains expressed until soon after wound closure is complete. In the respiratory epithelium, av136 mRNA expression is induced within 5 h of acute injury, and c~v136 protein can be detected in the epithelium of patients with a v...
