TY - JOUR

T1 - Hypohalous acid-modified human serum albumin induces neutrophil NADPH-oxidase activation, degranulation and shape change

AU - Gorudko, I.V.

AU - Grigorieva, D.V.

AU - Shamova, E.V.

AU - Kostevich, V.A.

AU - Sokolov, A.V.

AU - Mikhalchik, E.V.

AU - Cherenkevich, S.N.

AU - Arnhold, J.

AU - Panasenko, O.M.

PY - 2014

Y1 - 2014

N2 - Halogenated lipids, proteins, and lipoproteins formed in reactions with myeloperoxidase (MPO)-derived hypochlorous acid (HOCl) and hypobromous acid (HOBr) can contribute to the regulation of functional activity of cells and serve as mediators of inflammation. Human serum albumin (HSA) is the major plasma protein target of hypohalous acids. This study was performed to assess the potency of HSA modified by HOCl (HSA-Cl) and HOBr (HSA-Br) to elicit selected neutrophil responses. HSA-Cl/Br were found to induce neutrophil degranulation, generation of reactive oxygen intermediates, shape change, and actin cytoskeleton reorganization. Thus HSA-Cl/Br can initially act as a switch and then as a feeder of the "inflammatory loop" under oxidative stress. In HSA-Cl/Br-treated neutrophils, monoclonal antibodies against CD18, the β subunit of β2 integrins, reduced the production of superoxide anion radicals and hydrogen peroxide as well as MPO exocytosis, suggesting that CD18 contributed to neutrophil activation. HSA-Cl/Br-

AB - Halogenated lipids, proteins, and lipoproteins formed in reactions with myeloperoxidase (MPO)-derived hypochlorous acid (HOCl) and hypobromous acid (HOBr) can contribute to the regulation of functional activity of cells and serve as mediators of inflammation. Human serum albumin (HSA) is the major plasma protein target of hypohalous acids. This study was performed to assess the potency of HSA modified by HOCl (HSA-Cl) and HOBr (HSA-Br) to elicit selected neutrophil responses. HSA-Cl/Br were found to induce neutrophil degranulation, generation of reactive oxygen intermediates, shape change, and actin cytoskeleton reorganization. Thus HSA-Cl/Br can initially act as a switch and then as a feeder of the "inflammatory loop" under oxidative stress. In HSA-Cl/Br-treated neutrophils, monoclonal antibodies against CD18, the β subunit of β2 integrins, reduced the production of superoxide anion radicals and hydrogen peroxide as well as MPO exocytosis, suggesting that CD18 contributed to neutrophil activation. HSA-Cl/Br-

KW - Degranulation

KW - Free radicals

KW - Human neutrophil

KW - Human serum albumin

KW - Hypobromous acid

KW - Hypochlorous acid

KW - Myeloperoxidase

KW - Oxidative stress

U2 - 10.1016/j.freeradbiomed.2013.12.023

DO - 10.1016/j.freeradbiomed.2013.12.023

M3 - Article

VL - 68

SP - 326

EP - 334

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

ER -