HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print February 3, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0703317v1 75/5/836    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goepel, F. Articles by Walzog, B. Search for Related Content PubMed PubMed Citation Articles by Goepel, F. Articles by Walzog, B.

(Journal of Leukocyte Biology. 2004;75:836-843.)
© 2004 by Society for Leukocyte Biology

Identification of caspase-10 in human neutrophils and its role in spontaneous apoptosis

Friederike Goepel^*, Pamela Weinmann^*, Jürgen Schymeinsky and Barbara Walzog^,1

^* Department of Physiology, Freie Universität, Berlin, Germany; and
Department of Physiology, Ludwig-Maximilians-Universität, München, Germany

¹Correspondence: Department of Physiology, Ludwig-Maximilians-Universität München, Schillerstrasse 44, D-80336 München, Germany. E-mail: walzog{at}lrz.uni-muenchen.de

In the present study, we investigated the molecular mechanisms of spontaneous and tumor necrosis factor (TNF-)-mediated apoptosis of human polymorphonuclear neutrophils (PMN). Whereas TNF--mediated apoptosis was almost absent in the presence of the caspase-8 inhibitor Z-Ac-Ala-Glu-Val-Asp-7-fluoromethyl ketone (Z-AEVD-FMK), the inhibitor had no effect on spontaneous apoptosis, suggesting that spontaneous apoptosis was independent of caspase-8. Subsequently, we identified different isoforms of caspase-10 in human PMN and found high expression of caspase-10/b and/or -10/d and low expression of caspase-10/a and -10/c at the mRNA level. At the protein level, freshly isolated PMN showed high expression of caspase-10/b and -10/d as well as moderate expression of caspase-10/a and -10/c. Upon spontaneous apoptosis, caspase-10/b was down-regulated, which was accompanied by the appearance of a specific 47-kDa caspase-10/b cleavage product and an increased caspase-10 activity. In contrast, no down-regulation of caspase-10/a, -10/c, or -10/d was observed, suggesting that spontaneous apoptosis was associated with a differential activation of caspase-10/b. This was confirmed by the finding that spontaneous apoptosis was inhibited in the presence of Z-Ile-Glu-Thr-Asp (Z-IETD)-FMK, which blocks caspase-10. However, no down-regulation of caspase-10 isoforms was observed in the presence of TNF-, suggesting that caspase-10 was not involved in TNF--induced apoptosis. Taken together, our study demonstrates that spontaneous and TNF--mediated apoptosis of PMN have different molecular requirements. Whereas TNF--mediated apoptosis depends on the activation of caspase-8, spontaneous apoptosis requires the activation of caspase-10/b. This finding may reveal that PMN apoptosis in different (patho-) physiological settings results from distinct molecular mechanisms.

Key Words: polymorphonuclear neutrophil • tumor necrosis factor • Z-AEVD-FMK • Z-IETD-FMK • inflammation

This article has been cited by other articles:

				I. H. Engels, G. Totzke, U. Fischer, K. Schulze-Osthoff, and R. U. Janicke Caspase-10 Sensitizes Breast Carcinoma Cells to TRAIL-Induced but Not Tumor Necrosis Factor-Induced Apoptosis in a Caspase- 3-Dependent Manner Mol. Cell. Biol., April 1, 2005; 25(7): 2808 - 2818. [Abstract] [Full Text] [PDF]