Expression of alpha 6 beta 1 integrin, the laminin receptor, on subsets of normal murine lung fibroblasts and its upregulation by the inflammatory cytokines IFN-gamma and TNF-alpha.

The purpose of this investigation was to ascertain whether the alpha 6 integrin subunit was present on normal murine lung cells and fibroblasts, and if so, to determine the identity of the beta subunit coordinately expressed with alpha 6 and whether or not these integrin subunits could be regulated by cytokines. Previously, our laboratory isolated populations of Thy 1+ and Thy 1- fibroblasts from normal murine lung tissue. These cells differed in surface marker expression and in response to, and production of, pro-inflammatory cytokines. Research defining the properties of these two populations has led to the hypothesis that unique groups of fibroblasts exist within the murine lung. Though alpha 6 beta 1 is known to be expressed by platelets, lymphocytes, and epithelial cells, its presence and regulation on lung fibroblast subsets has not been explored. We now report the following findings: 1) the laminin receptor, alpha 6 beta 1, is present on 20-30% of freshly isolated normal murine lung cells in all three murine strains tested; 2) established Thy 1+ and Thy 1- murine lung fibroblast subsets and clones constitutively express alpha 6 beta 1 at varied levels; and 3) alpha 6 beta 1 expression on fibroblast lines and clones can be upregulated by treatment with IFN-gamma or TNF-alpha. Since these T cell and macrophage derived cytokines are known to be present during an inflammatory response, upregulation of alpha 6 beta 1 expression may facilitate recruitment and retention of lung fibroblasts in regions undergoing repair.(ABSTRACT TRUNCATED AT 250 WORDS)