Active and zymogen forms of granzyme B are constitutively released from cytotoxic lymphocytes in the absence of target cell engagement.

Abstract:

:Granzyme B (GrB) plays a well-established intracellular role in cytotoxic lymphocyte (CL)-mediated killing of abnormal cells; however, emerging evidence suggests that it participates in extracellular matrix remodeling and target cell destruction through anoikis. As these processes require the release of GrB from the CL into the extracellular environment, we examined the secretion of GrB from natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). We found that a proportion of GrB is constitutively secreted by both CTLs and NK cells in the absence of target cell engagement. In NK cells, the protease is primarily released in an active form through secretory granules. By contrast, T lymphocytes primarily secrete inactive GrB zymogen, bypassing the granules. The release of GrB through two routes from unconjugated CLs suggests that it functions outside the cell and may contribute to pathology in cases of immune dysregulation, such as familial hemophagocytic lymphohistiocytosis (FHL). Our findings also predict the existence of an extracellular activator of GrB.

journal_name

Immunol Cell Biol

authors

Prakash MD,Bird CH,Bird PI

doi

10.1038/icb.2008.98

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

249-54

issue

3

eissn

0818-9641

issn

1440-1711

pii

icb200898

journal_volume

87

pub_type

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