PMID- 7520777 OWN - NLM STAT- MEDLINE DCOM- 19940928 LR - 20220409 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 84 IP - 5 DP - 1994 Sep 1 TI - Tumor necrosis factor-alpha (TNF-alpha) potently enhances in vitro macrophage production from primitive murine hematopoietic progenitor cells in combination with stem cell factor and interleukin-7: novel stimulatory role of p55 TNF receptors. PG - 1528-33 AB - Tumor necrosis factor-alpha (TNF-alpha) is a bifunctional regulator of hematopoiesis, and its cellular responses are mediated by two distinct cell surface receptors. TNF-alpha generally inhibits the growth of primitive murine hematopoietic progenitor cells (Lin-Scal+) in response to multiple cytokine combinations, and the p75 TNF receptor is essential in signaling such inhibition. In the present study we show the reverse phenomenon in that TNF-alpha on the same progenitor cell population in combination with stem cell factor (SCF) and interleukin-7 (IL-7) through the p55 TNF receptor can recruit additional progenitors to proliferate. In contrast, TGF-beta 1, another bifunctional regulator of hematopoietic progenitor cell growth, completely blocked SCF plus IL-7-induced proliferation. TNF-alpha increased the number of responding progenitors, as well as the size of the colonies formed. The synergistic effects of TNF-alpha were seen at the single cell level, suggesting that its effects are directly mediated. Finally, whereas SCF plus IL-7 promoted primarily granulopoiesis, the addition of TNF-alpha switched the differentiation toward the production of almost exclusively macrophages. FAU - Fahlman, C AU - Fahlman C AD - Department of Immunology, Norwegian Radium Hospital, Montebello. FAU - Jacobsen, F W AU - Jacobsen FW FAU - Veiby, O P AU - Veiby OP FAU - McNiece, I K AU - McNiece IK FAU - Blomhoff, H K AU - Blomhoff HK FAU - Jacobsen, S E AU - Jacobsen SE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Cell Adhesion Molecules) RN - 0 (Hematopoietic Cell Growth Factors) RN - 0 (Interleukin-7) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Recombinant Proteins) RN - 0 (Stem Cell Factor) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Bone Marrow Cells MH - Cell Adhesion Molecules/pharmacology MH - Cell Differentiation/*drug effects MH - Cell Division/drug effects MH - Cells, Cultured MH - Dose-Response Relationship, Drug MH - Drug Synergism MH - Hematopoietic Cell Growth Factors/*pharmacology MH - Hematopoietic Stem Cells/*cytology/drug effects MH - Humans MH - Interleukin-7/*pharmacology MH - Kinetics MH - Macrophages/*cytology/drug effects MH - Mice MH - Mice, Inbred C57BL MH - Rats MH - Receptors, Tumor Necrosis Factor/drug effects/*physiology MH - Recombinant Proteins/pharmacology MH - Stem Cell Factor MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 1994/09/01 00:00 MHDA- 1994/09/01 00:01 CRDT- 1994/09/01 00:00 PHST- 1994/09/01 00:00 [pubmed] PHST- 1994/09/01 00:01 [medline] PHST- 1994/09/01 00:00 [entrez] AID - S0006-4971(20)77622-6 [pii] PST - ppublish SO - Blood. 1994 Sep 1;84(5):1528-33.