Myeloperoxidase Stimulates Neutrophil Degranulation.
Myeloperoxidase, heme enzyme of azurophilic granules in neutrophils, is released into the extracellular space in the inflammation foci. In neutrophils, it stimulates a dose-dependent release of lactoferrin (a protein of specific granules), lysozyme (a protein of specific and azurophilic granules), and elastase (a protein of azurophilic granules). 4-Aminobenzoic acid hydrazide, a potent inhibitor of peroxidase activity of myeloperoxidase, produced no effect on neutrophil degranulation. Using signal transduction inhibitors (genistein, methoxyverapamil, wortmannin, and NiCl2), we demonstrated that myeloperoxidase-induced degranulation of neutrophils resulted from enzyme interaction with the plasma membrane and depends on activation of tyrosine kinases, phosphatidylinositol 3-kinases (PI3K), and calcium signaling. Myeloperoxidase modified by oxidative/halogenation stress (chlorinated and monomeric forms of the enzyme) lost the potency to activate neutrophil degranulation.
Physics Faculty, Belarusian State University, Minsk, Belarus.
D V
DV
Grigorieva
Physics Faculty, Belarusian State University, Minsk, Belarus.
I V
IV
Gorudko
Institute of Experimental Medicine, St. Petersburg, Russia.|Scientific Research Institute of Physical-Chemical Medicine, Russian Federal Medical-Biological Agency, Moscow, Russia.
A V
AV
Sokolov
Institute of Experimental Medicine, St. Petersburg, Russia.|Scientific Research Institute of Physical-Chemical Medicine, Russian Federal Medical-Biological Agency, Moscow, Russia.
V A
VA
Kostevich
Institute of Experimental Medicine, St. Petersburg, Russia.
V B
VB
Vasilyev
Physics Faculty, Belarusian State University, Minsk, Belarus.
S N
SN
Cherenkevich
Scientific Research Institute of Physical-Chemical Medicine, Russian Federal Medical-Biological Agency, Moscow, Russia. o-panas@mail.ru.
O M
OM
Panasenko
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D005711:Gallopamil / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077191:Wortmannin
D000730:Androstadienes; D005711:Gallopamil; C022838:nickel chloride; D009532:Nickel; D019833:Genistein; D009195:Peroxidase; D019869:Phosphatidylinositol 3-Kinases; D010129:4-Aminobenzoic Acid; D000077191:Wortmannin
human neutrophils; myeloperoxidase; neutrophil degranulation; oxidative/halogenation stress; signaling systems