Studies of interferon as a regulator of hematopoietic cell proliferation

E. L. Raefsky, L. C. Platanias, N. C. Zoumbos, N. S. Young

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142 Scopus citations

Abstract

The presence of interferon (IFN) in normal bone marrow and its abnormal production in aplastic anemia suggest that IFN may have normal regulatory roles and implicates them in the pathophysiology of bone marrow failure. We studied the effects of recombinant IFN (r-IFN) on hematopoietic colony formation in methylcellulose cultures of human bone marrow. Both recombinant IFN-γ (r-IFN-γ) and recombinant IFN-α (r-IFN-α) were potent suppressors of myeloid (CFU-C-derived) colony formation, with 50% inhibition occurring at 291 U/ml for r-IFN-γ and 275 U/ml for r-IFN-α. Small amounts of r-IFN-γ acted synergistically with r-IFN-α; as little as 5 U/ml of r-IFN-γ increased inhibition of CFU-C-derived colony formation by r-IFN-α over threefold. Conversely, small amounts of r-IFN-α did not affect inhibition by r-IFN-γ. Inhibition by r-IFN was highly dependent on culture conditions: reduction of the fetal calf serum concentration from 30% to 20%, a change that did not alter the plating efficiency of control cultures, significantly enhanced the action of r-IFN-γ. Competition between positive hematopoietic factors and r-IFN was further demonstrated as increasing amounts of human placenta-conditioned media, used as a source of colony-stimulating activity, also partially blocked r-IFN inhibition. To determine if r-IFN could directly inhibit the proliferation of a progenitor cell, cells isolated from immature BFU-E-derived colonies, a population enriched for late erythroid progenitors and free of auxiliary cells, were tested; similar inhibition by r-IFN-γ was observed with these isolated erythroid progenitors as with total bone marrow CFU-E. Although small amounts of r-IFN-γ also increased inhibition of bone marrow CFU-E-derived colony formation by r-IFN-α, no synergy was demonstrable with isolated erythroid progenitor cells. Therefore, even though r-IFN can directly inhibit proliferation of a progenitor cell, auxiliary cells may be required for synergy between r-IFN-γ and r-IFN-α.

Original languageEnglish (US)
Pages (from-to)2507-2512
Number of pages6
JournalJournal of Immunology
Volume135
Issue number4
StatePublished - Dec 1 1985

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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