PMID- 7522623 OWN - NLM STAT- MEDLINE DCOM- 19941107 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 84 IP - 7 DP - 1994 Oct 1 TI - Human interleukin-4 enhances stromal cell-dependent hematopoiesis: costimulation with stem cell factor. PG - 2189-96 AB - Interleukin-4 (IL-4) has distinct hematopoietic activities, primarily as a costimulant with other cytokines to enhance colony formation of hematopoietic progenitors. We investigated the influence of IL-4 on stromal cell-supported long-term cultures (LTCs) of normal human bone marrow. Addition of IL-4 to LTCs of unseparated bone marrow or highly enriched CD34+ cells resulted in a significant increase of myeloid progenitors in the nonadherent, as well as in the stromal cell-adherent cell populations. In contrast, the total cell number was not influenced by IL-4, suggesting a selective effect on primitive progenitor cells. Cord blood cells or CD34+ bone marrow cells were incubated with stem cell factor (SCF) and/or IL-4 in stromal cell-free cultures. In these experiments, a twofold to fivefold increase of myeloid progenitor cells was observed in the presence of SCF and IL-4 as compared with SCF alone. Preincubation of the stromal cell cultures with IL-4 resulted in an enhanced adherence of CD34+ cells to the stromal layer. Secretion of hematopoietic growth factors produced by the stromal cells, such as granulocyte-macrophage colony-stimulating factor (G-CSF), and IL-1, was inhibited by IL-4. Thus, the increase of hematopoietic progenitors in LTCs, as observed in the presence of IL-4, can be at least partially explained by a costimulation of SCF and IL-4 on primitive progenitor cells and by an enhancement of hematopoietic cells to stroma. The downregulation of CSFs by IL-4 might prevent the expansion of the mature hematopoietic cell compartment. FAU - Keller, U AU - Keller U AD - Department of Medicine, Johannes-Gutenberg-University School of Medicine, Mainz, Germany. FAU - Aman, M J AU - Aman MJ FAU - Derigs, G AU - Derigs G FAU - Huber, C AU - Huber C FAU - Peschel, C AU - Peschel C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD) RN - 0 (Antigens, CD34) RN - 0 (Cytokines) RN - 0 (Hematopoietic Cell Growth Factors) RN - 0 (Interleukin-3) RN - 0 (Stem Cell Factor) RN - 207137-56-2 (Interleukin-4) SB - IM MH - Antigens, CD/analysis MH - Antigens, CD34 MH - *Bone Marrow Cells MH - Cell Adhesion/drug effects MH - Colony-Forming Units Assay MH - Cytokines/metabolism MH - Drug Synergism MH - Hematopoiesis/*drug effects MH - Hematopoietic Cell Growth Factors/*administration & dosage MH - Humans MH - In Vitro Techniques MH - Interleukin-3/pharmacology MH - Interleukin-4/*administration & dosage MH - Stem Cell Factor EDAT- 1994/10/01 00:00 MHDA- 1994/10/01 00:01 CRDT- 1994/10/01 00:00 PHST- 1994/10/01 00:00 [pubmed] PHST- 1994/10/01 00:01 [medline] PHST- 1994/10/01 00:00 [entrez] AID - S0006-4971(20)76500-6 [pii] PST - ppublish SO - Blood. 1994 Oct 1;84(7):2189-96.