INVOLVEMENT OF THE EXTRACELLULAR CALCIUM IN THE RELEASE OF ELASTASE AND THE HUMAN NEUTROPHILS OXIDATIVE BURST

Some proteases (particularly elastase) and metabolites of very reactiv e oxygen species (superoxide en peroxide, hypochlorous acid and hydrox yl radicals) are generated by polymorphonuclear neutrophils (PMNs) dur ing inflammatory disorders. Divalent cations, especially calcium (Ca2) play an important regulatory role in the different PMNs functions. T he aim of this study is to determine the role of extracellular calcium during the liberation of elastase and of reactive oxygen species prod uction by human PMNs. Consequently, in order to stimulate PMNs, phorbo lmyristate 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 producti on 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. W ith 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 (O -2(-)) generated by PMNs activated by fMLP is dependent from the extra cellular calcium in the medium, whereas O-2(-) production by PMA or OZ stimulated neutrophils was extracellular calcium-independent. These o bservations suggest that an influx of calcium may play an important ro le in the production of elastase and in the capacity of PMNs stimulate d by fMLP to produce O-2(-) to reverse the PMA and OZ systems.