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Association of serine protease with the rise of intracellular calcium in cytotoxic T lymphocytes.

Abstract：

:The precise role of the granular enzyme A (granzyme A), a serine protease, in the lytic process of cytotoxic T lymphocytes (CTL) is not clear. We have recently constructed a CTL line transfected with the antisense gene of granzyme A (a-GrA). These a-GrA CTL had lower GrA activity as well as decreased lytic activities, as measured by 51Cr and by DNA degradation assays. Furthermore, at low effector:target ratio (1:8) in prolonged lytic assays, they could not lyse targets as rapidly as the control CTL. When we examined their ability to exocytose BLT (CBZ-L-lys-thiobenzyl)-esterase in the presence of anti-CD3 antibody, the a-GrA CTL exocytosed poorly compared to the parental CTL or control transfectant with a CAT gene. Most strikingly, a-GrA cells could not release intracellular stores of Ca2+ in response to anti-CD3 induction, although the Ca2+ flux was normal when they were stimulated with ionomycin. When the parental CTL was treated with a specific benzyllactam inhibitor of BLT-esterase or N-tosyl-L-phenylalanylchloromethyl ketone, the Ca2+ flux induced by anti-CD3 was also suppressed. We propose that granzyme A is involved in the signal transduction pathway that causes the rise of the intracellular calcium.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Koo GC,Luk Y,Talento A,Wu J,Sirotina A,Fischer PA,Blake JT,Nguyen MP,Parsons W,Poe M

doi

10.1006/cimm.1996.0300

subject

Has Abstract

pub_date

1996-12-15 00:00:00

pages

107-15

issue

2

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(96)90300-7

journal_volume

174

pub_type

杂志文章

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