Growth Factors of Lower Vertebrates

Abstract

Colony-stimulating factor-1 (CSF-1) regulates mononuclear cell proliferation, differentiation, and survival. The functions of CSF-1 are well documented in mammals; however, little is known about CSF-1 biology in lower vertebrates. This is the first report on the identification and functional characterization of a fish CSF-1 molecule expressed highly in the spleen and in phorbol 12-myristate 13-acetate-stimulated monocytes. Goldfish CSF-1 is a 199-amino acid protein that possesses the required cysteine residues to form important intra-chain and inter-chain disulfide bonds that allow CSF-1 to form a functional homodimer and to interact with its high affinity receptor, CSF-1R. Recombinant goldfish CSF-1 formed a homodimer and bound to the soluble goldfish CSF-1R. The addition of the recombinant CSF-1 to sorted goldfish progenitor cells, monocytes, and macrophages induced the differentiation of monocytes into macrophages and the proliferation of monocyte-like cells. The proliferation of these cells was abrogated by addition of an anti-CSF-1R antibody as well as the soluble CSF-1R. The ability of the soluble CSF-1R to inhibit CSF-1-induced proliferation represents a novel mechanism for the regulation of CSF-1 function.Colony-stimulating factor-1 (CSF-1) 2 is the primary growth factor involved in the regulation of survival, proliferation, and differentiation of mononuclear phagocytes and their precursors (1). CSF-1 has also been demonstrated to play important roles in bone metabolism, atherogenesis, inflammation, pregnancy, and in pre-implantation development of the female reproductive tract (2-4). All forms of CSF-1 initiate their effects by a high affinity interaction between the CSF-1 molecule, which is commonly active as a homodimer, and the CSF-1 receptor (CSF-1R) which is a member of the class III receptor tyrosine kinase family (5-8).From an evolutionary standpoint, macrophages and their functions are quite conserved; macrophage-like cells can be found in almost all multicellular organisms. Macrophage development is relatively unknown in almost all of these organisms with the exception of mammals. Until recently, mammals were the only group of organisms in which CSF-1 had been identified, and the suggestion that the CSF-1 pathway of macrophage development existed in organisms other than mammals was the identification of CSF-1 transcripts in the chicken (9, 10) and fish (11-13) as well as the identification of a CSF-1R in the goldfish (14), pufferfish (15), rainbow trout (16), zebrafish (17), and the gilthead sea bream (18).Here we describe the identification and biological characterization of the first CSF-1 from a nonmammalian organism, the goldfish. Goldfish CSF-1 was encoded for by a 600-bp open reading frame that translates into a predicted peptide of 199 amino acids. Although it had only a 27% amino acid identity with human CSF-1, important cysteine residues required for formation of the CSF-1 homodimer were conserved. Goldfish CSF-1 was highly expressed in the spleen, and its expression was up-regulated i...

Gram-Negative Marine Bacteria: Structural Features of Lipopolysaccharides and Their Relevance for Economically Important Diseases

“…(6) Several studies in different fish species have pointed to the presence and central role of cytokines and chemokines, including tumor necrosis factor (TNF)-α and TNF-β, interferon (IFN), interleukin (IL)-6, IL-1β, and colony-stimulating factors (CSFs), which activate a diverse class of immune and tissue cells [125,126,127,128,129,130,131,132,133,134]. These various activating molecules boost phagocytosis and trigger cells to produce antiviral and antibacterial protein molecules that resist bacterial and viral insult through several cell-dependent and cell-independent mechanisms.…”

Mechanisms of amphibian macrophage development: characterization of the Xenopus laevis colony-stimulating factor-1 receptor

“…However, many other aspects of lower vertebrate macrophage biology appear to be distinct from what has been documented in mammals. This includes varying teleost CSF1 ligand and receptor gene copy numbers (Hanington et al , 2007; Wang et al ., 2008; Wang et al ., 2014; Williams et al ., 2002) and unique physiological localization of amphibian monopoiesis (Grayfer and Robert, 2013). It remains to be determined whether these differences arise from and/or are dependent on CSF1-CSF1R functions which are different to those of mammals.…”

“…Monopoiesis, or the development and differentiation of macrophage lineage cells is chiefly mediated by the colony stimulating factor-1 (CSF1; macrophage colony-stimulating factor, MCSF) cytokine and growth factor (Garceau et al ., 2010; Hanington et al ., 2007; Pixley and Stanley, 2004; Wang et al , 2008). CSF1 functions as a homo-dimer, ligating the high-affinity tyrosine kinase CSF1 receptor (CSF1R) (Dai et al ., 2002), the cell surface expression of which is restricted predominantly to mononuclear phagocytes and their derivative cell populations (Guilbert and Stanley, 1980; Lichanska et al ., 1999).…”

“…CSF1 is present in birds (Garceau et al ., 2010), amphibians (Grayfer and Robert, 2013), and bony fish (Hanington et al ., 2007); and CSF1Rs have been identified, in birds (Garceau et al ., 2010) and teleosts (Barreda et al ., 2005; Honda et al , 2005; How et al , 1996; Parichy et al ., 2000; Pettersen et al ., 2008). However, it appears that the bony fish CSF1 ligand-receptor axis is distinct to that of mammals (Hanington et al , 2007; Wang et al ., 2008; Wang et al ., 2014). Indeed, fish species possess multiple distinct gene copies of both the CSF1 ligand and receptor, which contrasts to single copies seen across higher vertebrates.…”

Amphibian macrophage development and antiviral defenses

“…Monopoiesis is controlled through binding of the principal macrophage growth factor, colony-stimulating factor-1 (CSF-1, macrophage-colony-stimulating factor, M-CSF; Garceau et al, 2010; Hanington et al, 2007; Pixley and Stanley, 2004; Wang et al, 2008) to its cognate receptor (CSF-1R; Dai et al, 2002), which is almost exclusively expressed on committed macrophage precursors and derivative phagocyte populations (Guilbert and Stanley, 1980; Lichanska et al, 1999). It is noteworthy that birds and mammals possess a single, alternatively spliced mRNA transcript, giving rise to membrane-bound and secretory forms of CSF-1 (Manos, 1988; Rettenmier and Roussel, 1988).…”