M-CSF receptors

The biologically active form of M-CSF is a homodimer (two identical subunits). These homodimers can exist as integral cell surface proteins, or may be released from their producer cell by proteolytic cleavage, thus yielding the soluble cytokine. The M-CSF receptor is a single-chain, heavily glycosylated, polypeptide of molecular mass 150 kDa. 

K. Chu, S. Doberstein, L. T. Williams, and D. Hollenbaugh, A novel cytokine, FTP025, regulates myeloid growth and differentiation via the M-CSF receptor, Blood 108, 191a (2006). 

Csflr M-CSF receptor Osteopetrosis without osteoclasts Macrophage deficiency, fertility defect... 

The chromosomal locations of IL-3 and its receptor are 5q23-31 (IL-3) in this area are located the genes of several hematopoietic growth factors, such as GM-CSF, M-CSF, and the M-CSF receptor (known as the c-fms oncogene) Ypl3.3, Xp22.3 (IL-3Ra-cham) and 22 (IL-3RP-chain). 

Fig. 2.1 Sequence of events in atherogenesis and role of low-density lipoprotein. Native LDL, in the subendothelial space, undergoes progressive oxidation (mmLDL) and activates the expression of MCP-1 and M-CSF in the endothelium (EC). MCP-1 and M-CSF promote the entry and maturation of monocytes to macrophages, which further oxidise LDL (oxLDL). Ox-LDL is specifically recognised by the scavenger receptor of macrophages and, once internalised, formation of foam cells occurs. Both mmLDL and oxLDL induce endothelial dysfunction, associated with changes of the adhesiveness to leukoc)des or platelets and to wall permeability.

FRUEBis J, GONZALEZ v, siLVESTRE M and PALiNSKi w (1997) Effect of probucol treatment on gene expression of VCAM-1, MCP-1, and M-CSF in the aortic wall of LDL receptor-deficient rabbits during early sihsro genss.is, Arteriosclerosis, Thrombosis and Vascular Biology 17, 1289-302. 

The proposed model to explain OCS is schematized in Fig. 7.2. Several agents, induced or not for estrogen deficiency, stimulate the expression of RANKL on stromal/OB cells. The binding of RANKL with its receptor RANK on osteoclastic precursors, together with M-CSF, is a necessary and sufficient condition to carry out all the steps in the formation and differentiation of the osteoclasts. Undoubtedly all this is much more complex than what is described here since at least 24 genes that positively and negatively regulate OCS have been described (Boyle et al. 2003). 

Fig. 7.3. Osteoclastogenesis after estrogen deficiency. Estrogen deprivation leads to an increase in the synthesis of RANKL for stromal/OB cells of the BM. This increase in the expression of RANKL leads to an increase in OCS. Estrogen deficiency also induces the synthesis and secretion of cytokines, such as IL-6 and M-CSF, that increase the number of preosteoclasts in the BM, and thus increases OCS. Nonetheless, certain cells of the immune system, such as monocytes and T-cells, intervene in the process when the supply of estrogens fails. These cells secrete IL-1 and TNF-a that are powerful inductors of OCS. When estrogens or agonists of estrogen receptors like raloxifene are administered, the synthesis and secretion of many of the mentioned cytokines diminish and the synthesis and liberation of OPG and TGF-/S are stimulated. These molecules inhibit OCS by inhibiting the RANKL/RANK signal pathway and by promoting osteoclast apoptosis...

Growth factors, which are produced both as soluble and membrane-bound isotype proteins include members of the receptor tyrosine kinase subclass 111, such as stem cell factor (SCF) (Anderson et al, 1990 Huang et al, 1990), colony stimulating factor-1 (CSF-1, M-CSF) (Ladner et al, 1988 Ceretti et al, 1988) and Fit 3 ligand (Hannum et al, 1994 McClanahan et al, 1996). 

The receptors for one of the colony-stimulating factors (M-CSF) and for platelet-derived growth factor (PDGF) are also membrane proteins with tyrosine kinase activity. Al-... 

Terashi K, Oka M, Ohdo S, et al. Close association between clearance of recombinant human granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor on neutrophils in cancer patients. Antimicrob. Agents Chemother. 1999 43 21-24. 

Terashi, K., Oka, M., Ohdo, S., Furukubo, T., Ikeda, C., Fukuda, M., Soda, H., Higuchi, S., and Kohno, S., Close association between clearance of recombinant human granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor on neutrophils in cancer patients, Antimicrobial Agents and Chemotherapy, Vol. 43, No. 1, 1999, pp. 21-24. 

Several cytokine receptors are present in prostate tumors and in prostate cancer cell lines. These include the granulocyte-macrophage colony-stimulating factor receptors (GM-CSF-R) and macrophage colony-stimulating factor receptor (M-CSF-R) (R7, RIO, S4). The presence of interleukin receptors in the prostate tumor which bind interleukins such as IL-2, IL-3, and IL-6 may play a role in hormone-dependent as well as in hormone-refractory prostate cancer tumors (Cl3, R6). However, the importance of these receptors needs to be illuminated. 

R10. Roklin, O. W., Griebling, T. L., Karassina, N. V., Raines, M. A., and Cohen, M. B., Human prostate carcinoma cell lines secrete GM-CSF and express GM-CSF-receptor on their cell surface. Anticancer Res. 16, 557—563 (1996). 

Woodcock, J. M., McClure, B. J., Stomski, F. C., Elliott, M.J., Bagley, C.J., and Lopez, A. F. (1997). The human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor exists as a preformed receptor complex that can be activated by GM-CSF, interleukin-3, or interleukin-5. Blood 90, 3005—3017. 

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