Differentiation of primary human fibroblasts into tissue macrophages by the Snyder-Theilen strain of the feline sarcoma virus is associated with endoreduplication, a 1,9 translocation, phenotypic stability, and apoptosis

Abstract

We have previously reported the conversion of human fibroblasts to tissue macrophages by transduction with the Snyder-Theilen feline sarcoma virus [ST:FeSV (FeLV)]. The ST:FeSV-induced macrophages were largely configured as spherical cells, each with an extensive network of microvilli. Nuclear alterations included the appearance of three sub-populations within these mononucleated macrophages consisting of diploid (19%), tetraploid (43%), and octaploid (38%) cells. A karyotypic analysis revealed a 1,9 translocation in a small, dividing, subpopulation within the diploid fraction of the ST:FeSV-induced macrophages. Clonotypic assays demonstrated the conversion of all individually expanded, cloned fibroblasts, to macrophages following transduction with ST:FeSV. None of the converted macrophages reverted to the fibroblastic cell phenotype as determined by co-expression of v-fes and the receptor for the macrophage colony stimulating factor (CSF-IR). The ST:FeSV-induced macrophages did not form colonies in agar, nor did they form tumors in athymic mice. They appeared to undergo apoptosis after 4-6 weeks in culture. The findings pertain to the heterogeneous nature of tissue macrophages and their recruitment process during normal conditions, and in response to inflammatory stimuli.