Regulation of plasminogen binding to neutrophils

Citation
T. Herren et al., Regulation of plasminogen binding to neutrophils, BLOOD, 97(4), 2001, pp. 1070-1078
Citations number
72
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
00064971 → ACNP
Volume
97
Issue
4
Year of publication
2001
Pages
1070 - 1078
Database
ISI
SICI code
0006-4971(20010215)97:4<1070:ROPBTN>2.0.ZU;2-B
Abstract
Plasminogen plays an integral role in the inflammatory response, and this p articipation is likely to depend on its interaction with cell surfaces. It has previously been reported that isolation of human neutrophils from blood leads to a spontaneous increase in their plasminogen-binding capacity, and the basis for this up-regulation has been explored as a model for mechanis ms for modulation of plasminogen receptor expression. Freshly isolated huma n peripheral blood neutrophils exhibited relatively low plasminogen binding , but when cultured for 20 hours, they increased this capacity dramatically , up to IO-fold, This increase was abolished by soybean trypsin inhibitor a nd was susceptible to carboxypeptidase B treatment, implicating proteolysis and exposure of carboxy-terminal lysines in the enhanced interaction, In s upport of this hypothesis, treatment of neutrophils with elastase, cathepsi n G, or plasmin increased their plasminogen binding, and specific inhibitor s of elastase and cathepsin G suppressed the up-regulation that occurred du ring neutrophil culture, When neutrophils were stimulated with phorbol este r, their plasminogen binding increased rapidly, but this increase was insen sitive to the protease inhibitors. These results indicate that plasminogen binding to neutrophils can be up-regulated by 2 distinct pathways. A major pathway with the propensity to markedly up-regulate plasminogen binding dep ends upon the proteolytic remodeling of the cell surface. In response to th ioglycollate, neutrophils recruited into the peritoneum of mice were shown to bind more plasminogen than those in peripheral blood, suggesting that mo dulation of plasminogen binding by these or other pathways may also occur i n vivo. (C) 2001 by The American Society of Hematology.