当前位置： SCI文献检索 > INTERNATIONAL IMMUNOPHARMACOLOGY期刊下所有文献 > Effect of a thiol proteinase inhibitor, E-64-d, on susceptibility to infection with Staphylococcus aureus in Chediak-Higashi syndrome (beige) mice.

Effect of a thiol proteinase inhibitor, E-64-d, on susceptibility to infection with Staphylococcus aureus in Chediak-Higashi syndrome (beige) mice.

Abstract：

:We previously reported that abnormally down-regulated protein kinase C (PKC) activity is responsible for the impaired cellular function of natural killer cells and polymorphonuclear cells (PMNs), and the giant granule formation in fibroblasts in the beige mouse, an animal model of Chediak-Higashi syndrome. Here, we examine the effect of oral or intraperitoneal administration of E-64-d, which protects PKC from calpain-mediated proteolysis, on the impaired cellular function in PMNs from beige mice. We found that oral administration of E-64-d (12.5 mg/kg body weight per day) for three consecutive days, significantly improved the abnormally increased concanavalin A (Con A) cap formation and the decreased lysosomal enzyme activity in beige PMNs. In addition, E-64-d significantly improved the delayed bactericidal activity against Staphylococcus aureus. In contrast, E-64-d at the same dose did not affect these cellular functions in PMNs from C57BL/6J mice. We confirmed that the abnormal down-regulation of PKC after Con A stimulation was eliminated in PMNs from E-64-d-treated beige PMNs. We then examined whether the administration of E-64-d to beige mice improved the susceptibility to experimental infection with S. aureus (2x10(8)/mouse). Both intraperitoneal and oral administration of E-64-d to beige mice resulted in a significant increase in survival, whereas E-64-d at the same dose did not alter the survival rate in normal mice. These results suggest that the administration of E-64-d may be effective against severe bacterial infection in Chediak-Higashi syndrome.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Morimoto M,Tanabe F,Kasai H,Ito M

doi

10.1016/j.intimp.2007.03.004

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

973-80

issue

7

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(07)00084-7

journal_volume

7

pub_type

杂志文章

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