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Leukocyte contribution to parenchymal cell death in an experimental model of inflammation
Author(s) -
Tung David K.L.,
Bjursten Lars M.,
Zweifach Benjamin W.,
SchmidSchönbein Geert W.
Publication year - 1997
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.62.2.163
Subject(s) - programmed cell death , leukocyte extravasation , biology , platelet activating factor , propidium iodide , intravital microscopy , inflammation , extravasation , immunology , apoptosis , microbiology and biotechnology , in vivo , biochemistry
The relationship between leukocyte migration and parenchymal cell death in vivo remains poorly documented. Accordingly, cell killing in the rat mesentery, as recorded by propidium iodide staining, was investigated with an intravital approach. Superfusion of platelet‐activating factor (PAF, 10 –8 M) or N ‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP, 10 –8 M) led to extensive leukocyte extravasation but no significant cell death. In contrast, pretreatment with 10 –8 M PAF or fMLP for 1 h, followed by superfusion of PAF in combination with fMLP (both at 10 –8 M) led to an increase in cell death. Mesenteric parenchymal cells but no endothelial cells were killed. Some of the dead cells were identified as granulocytes/monocytes that were already in the tissue at the start of the experiment. The incidence of cell death was lower but not eliminated when leukocyte migration was blocked with a monoclonal antibody against CD18. A xanthine oxidase inhibitor, BOF‐4272, failed to diminish cell death, whereas a hydroxyl radical scavenger, dimethylthiourea, attenuated cell killing without an effect on the number of adhering and migrating leukocytes. These observations demonstrate that leukocytes serve as a factor in the killing of extravascular cells only after the development of a level of stimulation that differs from that required to induce a migratory stimulus into the extravascular space. J. Leukoc. Biol. 62: 163–175; 1997.