Chymase inhibitor ameliorates eosinophilia in mice infected with Nippostrongylus brasiliensis.
BACKGROUND
Chymase is a chymotrypsin-like serine protease primarily stored in mast cells. Infection with helminth parasites is known to increase the level of mast cell chymase in the jejunum and serum in mice. The aim of the present study is to elucidate the role of chymase in helminth infection.


METHODS
Chymase inhibitor SUN-C8257 was administered to mice infected with the nematode Nippostrongylus brasiliensis, and the number of eosinophils in the blood, serum IgE levels and fecal egg counts were determined.


RESULTS
Administration of SUN-C8257 significantly inhibited blood eosinophilia in BALB/c mice infected with N. brasiliensis. The effect of SUN-C8257 was specific for eosinophils, in that it affected neither the number of total leukocytes nor serum IgE levels. SUN-C8257 did not alter the fecal egg counts in this model, showing that SUN-C8257 has no effect on infectivity and expulsion of the nematode. N. brasiliensis infection induced eosinophilia in mast cell-deficient mice (W/W(v)) as well as their littermates (+/+), and SUN-C8257 inhibited the eosinophilia in +/+ mice but not in W/W(v) mice. These results suggest that the eosinophil number may be regulated by different mechanisms in W/W(v) and +/+ mice, and that the effect of SUN-C8257 on nematode-induced eosinophilia is probably due to chymase inhibition.


CONCLUSIONS
Chymase released by activated mast cells may play a role in helminth-induced eosinophilia.
Watanabe
Naohiro
N
Department of Tropical Medicine, Jikei University School of Medicine, Tokyo, Japan.
Miura
Kenju
K
Fukuda
Yoshiaki
Y
D000818:Animals; D053818:Chymases; D004802:Eosinophilia / Q000188:drug therapy* / Q000209:etiology; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008407:Mast Cells / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D009559:Nippostrongylus; D010270:Parasite Egg Count; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017206:Strongylida Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D016896:Treatment Outcome
D015842:Serine Proteinase Inhibitors; D007073:Immunoglobulin E; D012697:Serine Endopeptidases; D053818:Chymases