Hepatocyte growth factor attenuates eotaxin and PGD2-induced chemotaxis of human eosinophils.
BACKGROUND
Hepatocyte growth factor (HGF) is known to influence a number of cell types, and regulate various biologic activities including cell migration, proliferation, and survival. In a recent study, we found that, in vivo, HGF suppresses allergic airway inflammation, i.e. the infiltration of inflammatory cells including eosinophils into the airway, and further, that HGF reduces Th2 cytokine levels; however, the directly physiologic role of HGF with eosinophils remains unclear. In this study, we investigate the potential of recombinant HGF to regulate the factor-induced chemotaxis of human eosinophils.


METHODS
Eosinophils were isolated from subjects with mild eosinophilia by modified CD16-negative selection. After culture with or without recombinant HGF, esoinophil chemotaxis was measured by Boyden chamber and KK chamber.


RESULTS
Treatment with HGF prevented eotaxin or prostaglandin D(2) (PGD(2))-induced chemotaxis of eosinophils. Moreover, we demonstrated that extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinases as well as the enhancement of Ca(2+) influx, which are indispensable for eosinophil chemotaxis, were attenuated by HGF treatment.


CONCLUSIONS
Taken together, these data suggest that in allergic diseases, HGF not only mediates eosinophils through the inhibition of Th2 cytokines, but also regulates the function of eosinophils directly, provides further insight into the cellular and molecular pathogenesis of allergic reactions.
Ito
W
W
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Akita, Japan.
Chiba
T
T
Kanehiro
A
A
Kato
H
H
Yamaguchi
K
K
Ueki
S
S
Kayaba
H
H
Chihara
J
J
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002633:Chemotaxis / Q000187:drug effects; D004802:Eosinophilia / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D015230:Prostaglandin D2; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*
C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D015230:Prostaglandin D2; D002118:Calcium; C036293:prostaglandin D2 receptor