Effects of cyclopentenone prostaglandins on myeloid cells during early infection with HTLV-I. I. Cell differentiation determines sensitivity to prostaglandins and virus infection

P. M. Lacal, A. Puglianiello, E. Bonmassar, C. D'Onofrio

Research output: Contribution to journalArticle


Human myeloid cell lines at different stages of differentiation (K562, HL60 and U937) were used to analyze the permissivity of the myelomonocytic lineage to acute infection with human T-cell leukemia virus type-I (HTLV-I) after cell-to-cell transmission and to evaluate the effect of cyclopentenone prostaglandins (PG)A1 and PGJ2 on virus transmission, proliferation of recipient cells and cell-mediated cytotoxicity against virus-donor cells. Exposure to HTLV-I delayed the growth rate of recipient cells, especially in U937 cells. This effect was related to the phase of cell cycle when cells were exposed to HTLV-I. Treatment of control and virus-exposed cells with these PGs, both inducing growth arrest prevalently at the G1/S interphase of the cell cycle, inhibited cell proliferation in a concentration-dependent way. The antiproliferative effect of both PGs increased progressively from pluripotent K562 to promyelocytic HL60 and monoblastoid U937 cells, suggesting that differentiated cells were more susceptible to PG-mediated inhibition of growth than pluripotent cells. PG treatment influenced the permissivity of recipient cells to HTLV-I, with different effects on less differentiated myeloid cells in comparison with more differentiated monoblastoid cells. In fact, the percentage of cells positive for the p19(gag) protein was increased among PG-treated K562 or HL60 cells, although it was reduced in PG-treated U937 cells. To this respect, PGA1 was more effective on asynchronous and PGJ2 on synchronous U937 cells. Interestingly, at early time points in asynchronous U937 cells, PG treatment increased the specific lysis of virus-donor cells toward the levels of untreated synchronous cells, suggesting that the phase of cell cycle influences the effector capacity of cells of the monocytic lineage. Because integration of proviral DNA is known to occur during the synthesis of DNA in dividing cells, the antiproliferative effect of PGA1 and PGJ2 on myelomonocytic cells, in particular on more differentiated cell types, contributes to reduce the infection of recipient cells during early virus transmission, possibly regulating both cell cycling and cell-mediated specific lysis of virus-donor cells.

Original languageEnglish
Pages (from-to)1086-1095
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
Publication statusPublished - 1994


ASJC Scopus subject areas

  • Pharmacology

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