PMID- 7884321 OWN - NLM STAT- MEDLINE DCOM- 19950413 LR - 20190516 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 57 IP - 3 DP - 1995 Mar TI - Differential regulation of fyn-associated protein tyrosine kinase activity by macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). PG - 484-90 AB - The proliferation and differentiation of macrophages are regulated by, among others, GM-CSF and M-CSF. Treatment of bone marrow nonadherent (NA) cells with M-CSF induced a greater percentage of NA cells into adherent cells, recognized as monocyte/macrophages, than did GM-CSF. The effect of GM-CSF and M-CSF on the activation of fyn kinase, a 59-kDa src family-related protein tyrosine kinase (PTK), was studied. Control cultures of bone marrow NA cells expressed only minimal levels of fyn kinase activity. Treatment of bone marrow NA cells with M-CSF, but not GM-CSF, for 12 to 24 h greatly enhanced the levels of fyn kinase activity. The effect of M-CSF on the activation of fyn kinase was further investigated using bipotential adherent bone marrow-derived macrophages (BMDMs) that coexpress receptors for both GM-CSF and M-CSF. BMDMs can be induced by either growth factor to undergo extensive proliferation in vitro. Compared to bone marrow NA cells, BMDMs displayed higher levels of basal fyn kinase activity, which were similarly elevated by M-CSF but not GM-CSF treatment. The role of fyn kinase in regulating cell adhesion was investigated by growing BMDMs in both tissue culture and Teflon flasks. The growth of BMDMs was anchorage independent; the majority of them continued to proliferate as cell suspension in Teflon flasks. Whereas the levels of fyn kinase activity in adherent BMDMs grown in tissue culture flasks increased steadily, those in BMDMs grown in Teflon flasks diminished. To study the role of fyn kinase in growth regulation, BMDMs were treated with c-fyn sense and antisense s-oligos. In the presence of c-fyn antisense s-oligos, the proliferative response of BMDMs to M-CSF but not GM-CSF was inhibited. In contrast, the proliferation of BMDM in response to either GM-CSF or M-CSF was not influenced by c-fyn sense s-oligos. Collectively, our data suggest that the activation of fyn kinase is closely associated with the acquisition of adherent capacity in maturing macrophages. FAU - Li, Y AU - Li Y AD - Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201. FAU - Chen, B AU - Chen B LA - eng GR - AI23499/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Oligonucleotides, Antisense) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Receptors, Granulocyte-Macrophage Colony-Stimulating Factor) RN - 0 (Recombinant Proteins) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor) RN - EC 2.7.10.2 (Fyn protein, mouse) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn) SB - IM GS - c-fyn MH - Animals MH - Base Sequence MH - Bone Marrow Cells MH - Cell Adhesion MH - Female MH - Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology MH - In Vitro Techniques MH - Macrophage Colony-Stimulating Factor/*pharmacology MH - Macrophages/*enzymology MH - Mice MH - Mice, Inbred C3H MH - Molecular Sequence Data MH - Oligonucleotides, Antisense/pharmacology MH - Protein-Tyrosine Kinases/*metabolism MH - Proto-Oncogene Proteins/*metabolism MH - Proto-Oncogene Proteins c-fyn MH - Receptor, Macrophage Colony-Stimulating Factor/metabolism MH - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism MH - Recombinant Proteins EDAT- 1995/03/01 00:00 MHDA- 1995/03/01 00:01 CRDT- 1995/03/01 00:00 PHST- 1995/03/01 00:00 [pubmed] PHST- 1995/03/01 00:01 [medline] PHST- 1995/03/01 00:00 [entrez] AID - 10.1002/jlb.57.3.484 [doi] PST - ppublish SO - J Leukoc Biol. 1995 Mar;57(3):484-90. doi: 10.1002/jlb.57.3.484.