PMID- 15978283 OWN - NLM STAT- MEDLINE DCOM- 20051027 LR - 20091119 IS - 0145-305X (Print) IS - 0145-305X (Linking) VI - 29 IP - 10 DP - 2005 TI - A novel soluble form of the CSF-1 receptor inhibits proliferation of self-renewing macrophages of goldfish (Carassius auratus L.). PG - 879-94 AB - Macrophage colony-stimulating factor (CSF-1) is the principal regulator of the survival, proliferation, and differentiation of macrophages and their precursors. CSF-1 activity is tightly controlled through mechanisms regulating gene expression of CSF-1 and its membrane-bound receptor (CSF-1R), as well as by receptor-mediated endocytosis, metabolic processing, and inhibition of downstream signaling. Herein we describe a novel mechanism for control of CSF-1 activity. Spontaneously growing goldfish (Carassius auratus L.) macrophages actively produced a soluble form of CSF-1R (sCSF-1R) that appears to compete for ligand binding with membrane CSF-1R. The sCSF-1R transcript encodes only for the ligand-binding portion of the receptor, but is derived from a full-length mRNA species as determined by sequence analysis. Gene expression was associated with decreased proliferation and differentiation of primary macrophages, decreased growth factor activity in culture supernatants, and marked phenotypic changes that culminated in apoptotic cell death. Recombinant sCSF-1R inhibited macrophage proliferation at nanomolar concentrations. Antibodies against recombinant sCSF-1R identified native sCSF-1R in primary macrophage culture supernatants and fish serum, and suggested the presence of endogenous mechanisms temporally regulating sCSF-1R release. This is the first report of a soluble CSF-1R and points to intrinsic mechanisms of hematopoietic control that may be conserved across evolution in discrete self-renewing macrophage populations. FAU - Barreda, Daniel R AU - Barreda DR AD - Department of Biological Science, University of Alberta, Edmonton, AB T6G 2E9, Canada. FAU - Hanington, Patrick C AU - Hanington PC FAU - Stafford, James L AU - Stafford JL FAU - Belosevic, Miodrag AU - Belosevic M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050407 PL - United States TA - Dev Comp Immunol JT - Developmental and comparative immunology JID - 7708205 RN - 0 (DNA, Complementary) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Proteins) RN - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Cell Proliferation MH - Cells, Cultured MH - Cloning, Molecular MH - DNA, Complementary/genetics MH - Gene Expression MH - Goldfish/genetics/*immunology MH - Kidney/cytology/immunology MH - Macrophages/classification/cytology/*immunology MH - Molecular Sequence Data MH - RNA, Messenger/genetics MH - Receptor, Macrophage Colony-Stimulating Factor/genetics/*immunology MH - Recombinant Proteins/genetics/immunology MH - Sequence Homology, Amino Acid MH - Solubility EDAT- 2005/06/28 09:00 MHDA- 2005/10/28 09:00 CRDT- 2005/06/28 09:00 PHST- 2004/11/10 00:00 [received] PHST- 2005/02/10 00:00 [accepted] PHST- 2005/06/28 09:00 [pubmed] PHST- 2005/10/28 09:00 [medline] PHST- 2005/06/28 09:00 [entrez] AID - S0145-305X(05)00025-X [pii] AID - 10.1016/j.dci.2005.02.006 [doi] PST - ppublish SO - Dev Comp Immunol. 2005;29(10):879-94. doi: 10.1016/j.dci.2005.02.006. Epub 2005 Apr 7.