Involvement of the extracellular calcium in the release of elastase and the human neutrophils oxidative burst.
Some proteases (particularly elastase) and metabolites of very reactive oxygen species (superoxide anion, hydrogen peroxide, hypochlorous acid and hydroxyl radicals) are generated by polymorphonuclear neutrophils (PMNs) during inflammatory disorders. Divalent cations, especially calcium (Ca2+) play an important regulatory role in the different PMNs functions. The aim of this study is to determine the role of extracellular calcium during the liberation of elastase and of reactive oxygen species production by human PMNs. Consequently, in order to stimulate PMNs, phorbolmyristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP) and opsonized zymosan (OZ) have been used. PMNs stimulated by OZ did not release elastase to reverse the PMA and fMLP systems. The production of elastase by PMNs stimulated by PMA to reverse the fMLP system is independent from the extracellular calcium, between 0.0 and 1.5 mM. With various higher concentrations of calcium, varying from 1.5 to 4.0 mM, the release of elastase by PMNs stimulated by PMA is extracellular calcium-dependent to reverse the fMLP system. The superoxide anion (O2-) generated by PMNs activated by fMLP is dependent from the extracellular calcium in the medium, whereas O2- production by PMA or OZ stimulated neutrophils was extracellular calcium-independent. These observations suggest that an influx of calcium may play an important role in the production of elastase and in the capacity of PMNs stimulated by fMLP to produce O2- to reverse the PMA and OZ systems.
Khalfi
F
F
Laboratoire de Pharmacologie, Pharmacocinétique Clinique, Faculté des Sciences, Pharmaceutiques et Biologiques, Lille, France.
Gressier
B
B
Brunet
C
C
Dine
T
T
Luyckx
M
M
Cazin
M
M
Cazin
J C
JC
D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000201:enzymology; D009895:Opsonin Proteins / Q000494:pharmacology; D017382:Reactive Oxygen Species; D016897:Respiratory Burst / Q000502:physiology*; D015054:Zymosan / Q000494:pharmacology
D009895:Opsonin Proteins; D017382:Reactive Oxygen Species; D004533:Egtazic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D019272:Leukocyte Elastase; D002118:Calcium