Internalization of proteinase 3 is concomitant with endothelial cell apoptosis and internalization of myeloperoxidase with generation of intracellular oxidants
(2001) In American Journal of Pathology 158(2). p.581-592- Abstract
- The important issue addressed by the studies presented here is the mechanism of neutrophil-mediated damage to endothelial and epithelial cells during inflammation. Binding of neutrophil-released granule proteins to endothelial cells may be involved in vascular damage in patients with inflammatory vascular diseases. We have determined whether granule proteins proteinase 3(PR3) and/or myeloperoxidase (MPO) are internalized into endothelial cells, as examined by UV light, confocal, and electron microscopy. Coincident induction of apoptosis and/or the generation of intracellular oxidants were monitored. The results indicate that human endothelial cells (human umbilical vein endothelial cells, human umbilical arterial endothelial cells, human... (More)
- The important issue addressed by the studies presented here is the mechanism of neutrophil-mediated damage to endothelial and epithelial cells during inflammation. Binding of neutrophil-released granule proteins to endothelial cells may be involved in vascular damage in patients with inflammatory vascular diseases. We have determined whether granule proteins proteinase 3(PR3) and/or myeloperoxidase (MPO) are internalized into endothelial cells, as examined by UV light, confocal, and electron microscopy. Coincident induction of apoptosis and/or the generation of intracellular oxidants were monitored. The results indicate that human endothelial cells (human umbilical vein endothelial cells, human umbilical arterial endothelial cells, human lung microvascular endothelial cells) internalize both PR3 and MPO, which are detected on the cell surface, in the cytoplasm, and possibly nuclear. Epithelial cells (small airway epithelial cells) internalized MPO but not PR3, implying that the mechanism of PR3 internalization may be cell-type specific and different from that of MPO. Internalization of PR3, but not MPO, correlated with activation of apoptosis. Internalization of MPO correlated with an increase in intracellular oxidant radicals. The requirement for the proteolytic activity of PR3 for the induction of apoptosis was examined by generating PR3-truncated fragments that did not contain the components of the catalytic triad. An apoptotic function was localized to the C-terminal portion of PR3. These studies reveal novel mechanisms by which the neutrophil granule proteins PR3 and MPO contribute to tissue injury at sites of inflammation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1121634
- author
- Yang, Jia Jin ; Preston, Gloria A. ; Pendergraft, William F. ; Segelmark, Mårten LU ; Heeringa, Peter ; Hogan, Susan L. ; Jennette, J. Charles and Falk, Ronald J.
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American Journal of Pathology
- volume
- 158
- issue
- 2
- pages
- 581 - 592
- publisher
- American Society for Investigative Pathology
- external identifiers
-
- pmid:11159195
- scopus:0035135617
- ISSN
- 1525-2191
- language
- English
- LU publication?
- yes
- id
- f29e4387-e6f8-45a6-9706-74b099de4b8c (old id 1121634)
- alternative location
- http://ajp.amjpathol.org/cgi/content/full/158/2/581
- date added to LUP
- 2016-04-01 11:36:01
- date last changed
- 2022-04-20 19:02:57
@article{f29e4387-e6f8-45a6-9706-74b099de4b8c,
abstract = {{The important issue addressed by the studies presented here is the mechanism of neutrophil-mediated damage to endothelial and epithelial cells during inflammation. Binding of neutrophil-released granule proteins to endothelial cells may be involved in vascular damage in patients with inflammatory vascular diseases. We have determined whether granule proteins proteinase 3(PR3) and/or myeloperoxidase (MPO) are internalized into endothelial cells, as examined by UV light, confocal, and electron microscopy. Coincident induction of apoptosis and/or the generation of intracellular oxidants were monitored. The results indicate that human endothelial cells (human umbilical vein endothelial cells, human umbilical arterial endothelial cells, human lung microvascular endothelial cells) internalize both PR3 and MPO, which are detected on the cell surface, in the cytoplasm, and possibly nuclear. Epithelial cells (small airway epithelial cells) internalized MPO but not PR3, implying that the mechanism of PR3 internalization may be cell-type specific and different from that of MPO. Internalization of PR3, but not MPO, correlated with activation of apoptosis. Internalization of MPO correlated with an increase in intracellular oxidant radicals. The requirement for the proteolytic activity of PR3 for the induction of apoptosis was examined by generating PR3-truncated fragments that did not contain the components of the catalytic triad. An apoptotic function was localized to the C-terminal portion of PR3. These studies reveal novel mechanisms by which the neutrophil granule proteins PR3 and MPO contribute to tissue injury at sites of inflammation.}},
author = {{Yang, Jia Jin and Preston, Gloria A. and Pendergraft, William F. and Segelmark, Mårten and Heeringa, Peter and Hogan, Susan L. and Jennette, J. Charles and Falk, Ronald J.}},
issn = {{1525-2191}},
language = {{eng}},
number = {{2}},
pages = {{581--592}},
publisher = {{American Society for Investigative Pathology}},
series = {{American Journal of Pathology}},
title = {{Internalization of proteinase 3 is concomitant with endothelial cell apoptosis and internalization of myeloperoxidase with generation of intracellular oxidants}},
url = {{http://ajp.amjpathol.org/cgi/content/full/158/2/581}},
volume = {{158}},
year = {{2001}},
}