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Scleroderma-derived human fibroblasts retain abnormal phenotypic and functional characteristics following retroviral transduction with the SV40 tsT antigen.

Abstract：

:In this study an amphotropic retrovirus has been used to efficiently transduce normal human (NF) and scleroderma (systemic sclerosis; SSc) dermal fibroblasts (SScF) with a sequence encoding a temperature-sensitive mutant of the SV40 large T antigen (tsA58-U19). From the primary outgrowths of skin explants, cultures were generated whose growth was stringently temperature-dependent. When grown at a low, permissive temperature (35 degrees C), both normal and SSc-transduced cells continuously divided with similar doubling times, whereas at a high, nonpermissive temperature (39.5 degrees C), division of both the NF and SScF cells was rapidly arrested. These cells have been passaged more than 50 times, have the typical morphological appearance of fibroblasts, and have retained an anchorage-dependent phenotype. The transduced normal cells (tsT-NF) synthesized the matrix molecules collagen and fibronectin and expressed phenotypic antigens characteristic of their nontransduced counterparts, including MHC Class I, VLA beta 1 (CD29), Hermes 1 (CD44), VLA-4 alpha (CD49d), ICAM-1 (CD54) and LFA-3 (CD58) and the cell surface ectoenzymes neutral endopeptidase (CD10), aminopeptidase N (CD13), and dipeptidyl peptidase IV (CD26). Analysis of the transduced SSc fibroblasts (tsT-SScF) showed that these cells exhibited certain major features of the SSc pathology, notably the abnormally high synthesis of type I collagen, increased expression of ICAM-1, and depressed levels of CD26. Moreover, these phenotypic characteristics were retained even after prolonged culture in vitro. The tsT-SScF cells also retained their responsiveness to cytokines, since interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) both produced a marked increase in ICAM-1 expression. Our findings show that infection of SScF with the SV40 tsT antigen extends the life span of these cells and does not ablate their abnormal phenotypic and functional characteristics.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Xu S,Vancheeswaran R,Bou-Gharios G,O'Hare MJ,Olsen I,Abraham D,Black C

doi

10.1006/excr.1995.1332

subject

Has Abstract

pub_date

1995-10-01 00:00:00

pages

407-14

issue

eissn

0014-4827

issn

1090-2422

pii

S0014482785713328

journal_volume

220

pub_type

杂志文章

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Scleroderma-derived human fibroblasts retain abnormal phenotypic and functional characteristics following retroviral transduction with the SV40 tsT antigen.