Decreased functional caspase-3 expression in umbilical cord blood neutrophils is linked to delayed apoptosis

Resolution of inflammatory processes depends on the efficient removal of aging neutrophils by the reticuloendothelial system. Neutrophil apoptosis is key to this process, and its impairment may contribute to the pathogenesis of chronic inflammation. We recently discovered that Fas-mediated apoptosis in umbilical cord blood neutrophils was significantly delayed as compared with those of adults. Because execution of apoptosis relies on caspases, we used reverse transcription PCR, immunoblots, and enzymatic assays to study the integrity of several members of those proteases known to mediate Fas-induced apoptosis in neutrophils. Our results indicate that diminished expression of caspase-3 mRNA and the precursor form of the protein, as well as a lower functional enzymatic activity of caspase-3, correlates with delayed apoptosis in umbilical cord blood neutrophils. Our data suggest that functional expression of caspase-3 in neutrophils may be regulated during ontogeny.