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)
Cancer Center, University of Rochester School of Medicine and Dentistry, NY 14642-8704.
M E
ME
Felch
R A
RA
Willis
D P
DP
Penney
P C
PC
Keng
R P
RP
Phipps
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001483:Base Sequence; D016207:Cytokines / Q000494:pharmacology; D005347:Fibroblasts; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D017474:Receptors, Laminin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D018800:Thy-1 Antigens; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000954:Antigens, Surface; D016207:Cytokines; D016023:Integrins; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D017474:Receptors, Laminin; D011994:Recombinant Proteins; D018800:Thy-1 Antigens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma