Altered interaction of human granulation-tissue fibroblasts with fibronectin is regulated by alpha 5 beta 1 integrin.
Granulation-tissue fibroblasts express an unique phenotype distinct from normal fibroblasts. Due to the importance of the cell-matrix interactions in the regulation of cell morphology and behavior, we have compared the cell adhesion apparatus, especially integrin-type receptors, in fibroblasts cultured from healthy human periodontal connective tissues and from chronic and wound granulation tissues. The spreading of granulation-tissue cells on fibronectin, but not on type I collagen or laminin, was slower when compared with the normal fibroblasts. Cell spreading on fibronectin could be inhibited by RGD-containing peptide, suggesting integrin-mediated interaction. Both cell types expressed beta 1 integrin subunit, which associated with several integrin alpha subunits, namely alpha 1, alpha 2, alpha 3, alpha 5 and alpha v. In addition to beta 1 subunit, alpha v chain formed heterodimers with beta 3 and beta 5 subunits. Thus, these cells have multiple putative fibronectin, laminin, collagen, and vitronectin receptors. Cell spreading of both cell types on fibronectin was inhibited with anti-beta 1 and anti-alpha 5 antibodies, but antibodies against other putative FN-binding integrins (alpha 3, alpha v, and alpha v beta 3) had no effects. Furthermore, granulation-tissue fibroblasts showed delayed spreading on substrates coated with anti-beta 1 or anti-alpha 5 integrin antibodies. On substrates coated with anti-alpha 3 antibody, both cell types spread equally well. By FACS analysis, the amount of beta 1 and alpha 5 integrin subunits expressed on the cell surfaces was slightly elevated in GTFs compared with HGFs. Thus, the findings in this study indicate that the weakened interaction of granulation-tissue fibroblasts with fibronectin is regulated by altered function of alpha 5 beta 1 integrin.
Häkkinen
L
L
Department of Oral Biology, University of Turku, Finland.
Heino
J
J
Koivisto
L
L
Larjava
H
H
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology / Q000378:metabolism; D006097:Granulation Tissue / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D017469:Receptors, Fibronectin / Q000032:analysis
D005353:Fibronectins; D016023:Integrins; D017469:Receptors, Fibronectin