Characterization of a functional relationship between hepatocyte growth factor and mouse bone marrow-derived mast cells

Authors

  • Christine C. Fehlner-Gardiner,

    1. Department of Microbiology and Immunology, and the John P. Robarts Research Institute, University of Western Ontario, 100 Perth Drive, London, Ontario, Canada N6A5K8, e-mail: bosco@rri.on.ca, Tel.: +1-519-685 8300 ext. 34206, Fax: +1-519-663-3789
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  • Henian Cao,

    1. Department of Microbiology and Immunology, and the John P. Robarts Research Institute, University of Western Ontario, 100 Perth Drive, London, Ontario, Canada N6A5K8, e-mail: bosco@rri.on.ca, Tel.: +1-519-685 8300 ext. 34206, Fax: +1-519-663-3789
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  • Linda Jackson-Boeters,

    1. Department of Microbiology and Immunology, and the John P. Robarts Research Institute, University of Western Ontario, 100 Perth Drive, London, Ontario, Canada N6A5K8, e-mail: bosco@rri.on.ca, Tel.: +1-519-685 8300 ext. 34206, Fax: +1-519-663-3789
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  • Toshikazu Nakamura,

    1. Biomedical Research Center, Osaka University Medical School, Osaka, Japan
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  • Bruce E. Elliott,

    1. Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada
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  • Shashi Uniyal,

    1. Department of Microbiology and Immunology, and the John P. Robarts Research Institute, University of Western Ontario, 100 Perth Drive, London, Ontario, Canada N6A5K8, e-mail: bosco@rri.on.ca, Tel.: +1-519-685 8300 ext. 34206, Fax: +1-519-663-3789
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  • B. M. C. Chan

    1. Department of Microbiology and Immunology, and the John P. Robarts Research Institute, University of Western Ontario, 100 Perth Drive, London, Ontario, Canada N6A5K8, e-mail: bosco@rri.on.ca, Tel.: +1-519-685 8300 ext. 34206, Fax: +1-519-663-3789
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Abstract

During the early stage (at 4 weeks) of interleukin-3 (IL-3)-induced development, mouse bone marrow-derived mast cells (BMMC) express α4, α5 and α6 integrins, whereas with further maturation beyond 10 weeks, only α5 integrin remains stably expressed. Hepatocyte growth factor (HGF) modulates the growth and movement of diverse cell types upon binding to its receptor, encoded by the proto-oncogene c-met. We report here the expression of c-met by BMMC throughout the course of their development. In addition, HGF stimulated migration of early week-4 BMMC, but not of the later stage week-10 BMMC, on fibronectin and laminin substrates. The developmental stage-dependent effect of HGF on BMMC was due to specific stimulation of the migratory function of α4 and α6, but not α5 integrins. In addition, HGF had no effect on BMMC growth, either alone or in combination with IL-3. While HGF is stimulatory of the migratory function of BMMC, our results show that BMMC in turn can modulate HGF function. Thus, upon activation via the IgE receptors, BMMC released proteases that abolished HGF activities. Analyses of the degradation products by two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot using antisera prepared against recombinant HGF and the kringle 3 domain of HGF revealed specific degradation of HGF α but not β/β’ subunits. Therefore, our results suggest that: 1) the motogenic effect of HGF on BMMC varies according to the stage of their development, 2) HGF stimulation of BMMC migration is due to selective activation of α4 and α6, but not α5 integrin function, and 3) there exists a two-way relationship between BMMC and HGF such that HGF stimulates the β1 integrin-mediated migratory function of BMMC, which can, in turn, modulate HGF function by release of serine proteases.

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