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Effect of serine proteinase inhibitors on neutrophil function: α‐1‐proteinase inhibitor, antichymotrypsin, and a recombinant hybrid mutant of antichymotrypsin (LEX032) modulate neutrophil adhesion interactions
Author(s) -
Carney David F.,
Jagels Mark A.,
Hugli Tony E.,
Sands Howard,
Rubin Harvey
Publication year - 1998
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.63.1.75
Subject(s) - serpin , neutrophil elastase , proteolysis , proteases , biology , proteinase 3 , neutrophil extracellular traps , elastase , cathepsin g , serine proteinase inhibitors , adhesion , extracellular matrix , fibronectin , biochemistry , protease inhibitor (pharmacology) , protease , serine protease , microbiology and biotechnology , immunology , chemistry , inflammation , myeloperoxidase , enzyme , gene , human immunodeficiency virus (hiv) , antiretroviral therapy , viral load , organic chemistry
Circulating serine proteinase inhibitors (serpins) regulate a number of proteinases that participate in the inflammatory process. In this study, we investigated possible modulatory effects of serpins on neutrophil adhesion. Antichymotrypsin (ACT), α1‐protease inhibitor (α1‐PI), and LEX032, a recombinant hybrid of ACT and α1‐PI were shown to inhibit neutrophil adhesion to fibronectin (FN)‐coated surfaces and, to a lesser extent, adhesion to other extracellular matrix proteins. The inhibitory effect of serpins on neutrophil adhesion to FN was found to be related to inhibition of FN proteolysis based on the following observations: (1) elastase treatment of FN‐coated plates, but not of neutrophils, resulted in enhanced neutrophil adhesion; and (2) serpins inhibited FN proteolysis by neutrophil proteases. Serpins also inhibited neutrophil spreading, as well as shedding of neutrophil CD43, but not L‐selectin, CD18, or CD29. We conclude that serpins modulate neutrophil adhesion both by inhibiting proteolytic processing of extracellular matrix proteins and proteolytic shedding of CD43. J. Leukoc. Biol . 63: 75–82; 1998.