Ionomycin-induced neutrophil NADPH oxidase activity is selectively inhibited by the serine protease inhibitor diisopropyl fluorophosphate.

Dahlgren, Claes,1949Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för reumatologi och inflammationsforskning,Institute of Internal Medicine, Dept of Rheumatology and Inflammation Research (author)

The calcium-specific ionophore ionomycin triggers neutrophils to activate their NADPH oxidase and generate reactive oxygen species. This activation is restricted to intracellular sites and involves the neutrophil granules. Cells that have experienced an ionomycin-induced rise in intracellular calcium will also mobilize their intracellular granules and are primed to subsequent challenge with the chemoattractant formylmethionyl-leucyl-phenylalanine (fMLF), but have lost their ability to become desensitized to the same agonist. We have investigated the involvement of serine proteases in the calcium-induced effector functions using the inhibitor diisopropyl fluorophosphate (DFP). The ionomycin-induced NADPH oxidase activity was abrogated by the protease inhibitor, whereas the activity induced by fMLF was unaffected. The DFP-dependent inhibition was restricted to the NADPH oxidase activity, as all other ionomycin-induced cellular activities were largely unaffected. We thus suggest that a serine protease is of importance for the calcium ionophore-induced signal(s) to reach and activate the dormant NADPH oxidase in the neutrophil granules.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Immunologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Immunology in the medical area hsv//eng
Cell-Free System
Humans
Hydrogen Peroxide
pharmacology
Ionomycin
pharmacology
Ionophores
pharmacology
Isoflurophate
pharmacology
Luminescent Measurements
N-Formylmethionine Leucyl-Phenylalanine
pharmacology
NADPH Oxidase
metabolism
Neutrophils
enzymology
metabolism
Oxygen
metabolism
Phagocytosis
Reactive Oxygen Species
Serine
metabolism
Serine Proteinase Inhibitors
pharmacology
Subcellular Fractions
metabolism
Superoxides
Time Factors

Karlsson, Anna,1967Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för reumatologi och inflammationsforskning,Institute of Internal Medicine, Dept of Rheumatology and Inflammation Research(Swepub:gu)xkannb (author)
Göteborgs universitetInstitutionen för invärtesmedicin, Avdelningen för reumatologi och inflammationsforskning (creator_code:org_t)

In:Antioxidants & redox signaling: Mary Ann Liebert Inc4:1, s. 17-251523-08641557-7716

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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