Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
???displayArticle.abstract???
Immune cell recruitment is critical step in the inflammatory response and associated diseases. However, the underlying regulatory mechanisms are poorly understood in invertebrates. Mesenchyme cells of the starfish larvae, which allowed Metchnikoff to complete his landmark experiments, are important model for analysis of immune cell migration. The present study investigated the role of macrophage migration inhibitory factor (MIF)--an evolutionarily conserved cytokine that is functionally similar to chemokines--in the larvae of the starfish Patiria (Asterina) pectinifera, which were found to possess two orthologs, ApMIF1 and ApMIF2. ApMIF1 and ApMIF2 clustered with mammalian MIF and its homolog D-dopachrome tautomerase (DDT), respectively, in the phylogenetic analysis. In contrast to the functional similarity between mammalian MIF and DDT, ApMIF1 knockdown resulted in the excessive recruitment of mesenchyme cells in vivo, whereas ApMIF2 deficiency inhibited the recruitment of these cells to foreign bodies. Mesenchyme cells migrated along a gradient of recombinant ApMIF2 in vitro, whereas recombinant ApMIF1 completely blocked ApMIF2-induced directed migration. Moreover, the expression patterns of ApMIF1 and ApMIF2 messenger RNA in bacteria-challenged mesenchyme cells were consistent with in vivo observations of cell behaviors. These results indicate that ApMIF1 and ApMIF2 act as chemotactic inhibitory and stimulatory factors, respectively, and coordinately regulate mesenchyme cell recruitment during the immune response in starfish larvae. This is the first report describing opposing functions for MIF- and DDT-like molecules. Our findings provide novel insight into the mechanisms underlying immune regulation in invertebrates.
Bernhagen,
MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment.
2007, Pubmed
Bernhagen,
MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment.
2007,
Pubmed
Coleman,
Cooperative regulation of non-small cell lung carcinoma angiogenic potential by macrophage migration inhibitory factor and its homolog, D-dopachrome tautomerase.
2008,
Pubmed
DeVries,
Defining the origins and evolution of the chemokine/chemokine receptor system.
2006,
Pubmed
,
Echinobase
Fan,
Macrophage migration inhibitory factor and CD74 regulate macrophage chemotactic responses via MAPK and Rho GTPase.
2011,
Pubmed
Furukawa,
Starfish ApDOCK protein essentially functions in larval defense system operated by mesenchyme cells.
2012,
Pubmed
,
Echinobase
Furukawa,
Defense system by mesenchyme cells in bipinnaria larvae of the starfish, Asterina pectinifera.
2009,
Pubmed
,
Echinobase
Furukawa,
Characterization of a scavenger receptor cysteine-rich-domain-containing protein of the starfish, Asterina pectinifera: ApSRCR1 acts as an opsonin in the larval and adult innate immune systems.
2012,
Pubmed
,
Echinobase
Gregory,
Reduced leukocyte-endothelial cell interactions in the inflamed microcirculation of macrophage migration inhibitory factor-deficient mice.
2004,
Pubmed
Kiehart,
Microinjection of echinoderm eggs: apparatus and procedures.
1982,
Pubmed
,
Echinobase
Kraemer,
MIF-chemokine receptor interactions in atherogenesis are dependent on an N-loop-based 2-site binding mechanism.
2011,
Pubmed
Ley,
Getting to the site of inflammation: the leukocyte adhesion cascade updated.
2007,
Pubmed
Li,
A macrophage migration inhibitory factor like gene from scallop Chlamys farreri: Involvement in immune response and wound healing.
2011,
Pubmed
Merk,
The D-dopachrome tautomerase (DDT) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF).
2011,
Pubmed
Reif,
The CDM protein DOCK2 in lymphocyte migration.
2002,
Pubmed
Sai,
Parallel phosphatidylinositol 3-kinase (PI3K)-dependent and Src-dependent pathways lead to CXCL8-mediated Rac2 activation and chemotaxis.
2008,
Pubmed
Santos,
Macrophage migration inhibitory factor regulates neutrophil chemotactic responses in inflammatory arthritis in mice.
2011,
Pubmed
Sato,
Macrophage migration inhibitory factor (MIF) of jawed and jawless fishes: implications for its evolutionary origin.
2003,
Pubmed
Schulte,
Cytokines in sepsis: potent immunoregulators and potential therapeutic targets--an updated view.
2013,
Pubmed
Silva,
The onset of phagocytosis and identity in the embryo of Lytechinus variegatus.
2000,
Pubmed
,
Echinobase
Tamboline,
Secondary mesenchyme of the sea urchin embryo: ontogeny of blastocoelar cells.
1992,
Pubmed
,
Echinobase
Tamura,
MEGA6: Molecular Evolutionary Genetics Analysis version 6.0.
2013,
Pubmed
Tillmann,
Arrest Functions of the MIF Ligand/Receptor Axes in Atherogenesis.
2013,
Pubmed
Vermeire,
Orthologs of macrophage migration inhibitory factor from parasitic nematodes.
2008,
Pubmed
Weber,
Structural determinants of MIF functions in CXCR2-mediated inflammatory and atherogenic leukocyte recruitment.
2008,
Pubmed
Xin,
The MIF homologue D-dopachrome tautomerase promotes COX-2 expression through β-catenin-dependent and -independent mechanisms.
2010,
Pubmed
Zicha,
Are growth factors chemotactic agents?
1995,
Pubmed
