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* Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, Aberdeen, United Kingdom; and
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
Mammalian macrophage CSF (MCSF; CSF-1) is the primary regulator of the mononuclear phagocyte lineage. We, for the first time, report the complete sequencing of five MCSF cDNAs from three fish species, rainbow trout, zebrafish, and goldfish. Despite the difference in the lengths of the MCSF transcripts, all of the fish MCSF molecules encode a signal peptide, a CSF-1 domain, a transmembrane domain, and an intracellular region. Each fish MCSF gene has a unique exon/intron structure. The primordial MCSF gene may have had a nine exon/eight intron structure. In this model, insertion of an intron in exon 6 in primitive fish created the fish type I MCSF, while the loss of this exon or part of the original exon 6 created the fish type II MCSF. Investigation of alternative splicing variants in trout suggests that no mammalian equivalent splice variants exist. The two trout MCSF genes are differentially expressed in vivo and contributed differently to the high-level expression of MCSF in spleen and head kidney. In contrast to the up-regulation of MCSF by PMA in mammals, in trout MCSF1 expression is down-regulated by PMA treatment. As in mammals, recombinant trout MCSF1 can promote the growth of head kidney leukocytes, and it up-regulates the expression of CXCR3 in head kidney macrophages, with the latter suggesting a role of MCSF in the trafficking of macrophages to sites of inflammation or injury where the CXCR3 ligands are expressed. Thus MCSF has an important role in the immune system of fish as in mammals.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported financially by European Commission Contracts 513692 (Aquafirst), Q5RS-2001-002211 (Stressgenes), and 007103 (IMAQUANIM—Improved immunity of aquacultured animals).
2 The nucleotide sequences presented in this article have been submitted to the European Molecular Biology Laboratory/DNA Data Bank of Japan/GenBank nucleotide sequence database under the accession numbers AJ555867 (trout MCSF1 cDNA), AM901600 (trout MCSF1 DNA), AM949839 (trout MCSF2 cDNA), AM949840 (trout MCSF2 DNA), AM901598 (zebrafish MCSF1 cDNA), AM901599 (zebrafish MCSF2 cDNA), and AM982798 (goldfish MCSF cDNA).
3 Address correspondence and reprint requests to Dr. Christopher J. Secombes, Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, Aberdeen AB24 2TZ, U.K. E-mail address: c.secombes{at}abdn.ac.uk
4 Abbreviations used in this paper: MCSF, macrophage CSF; Ch, chromosome; CHO, Chinese hamster ovary; EST, expressed sequence tag; Mb, megabase; MCSFR, MCSF receptor; poly(I:C), polyinosinic:polycytidylic acid; rtMCSF, recombinant trout MCSF; UTR, untranslated region.
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  T. Wang, S. Bird, A. Koussounadis, J. W. Holland, A. Carrington, J. Zou, and C. J. Secombes Identification of a Novel IL-1 Cytokine Family Member in Teleost Fish J. Immunol., July 15, 2009; 183(2): 962 - 974. [Abstract] [Full Text] [PDF]
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