The loss of Mcl-1 expression in human polymorphonuclear leukocytes promotes apoptosis

The regulation of polymorphonuclear leukoctye (PMN) apoptosis can influence the duration of the inflammatory response. We have previously shown that P MN apoptosis is delayed by matrix adhesion lid hypoxia; however, the mechan isms responsible for this delay are not well understood. Mcl-1, an antiapop totic Bcl-2 family member, is present in neutrophils; therefore, we sought to characterize its localization and function as it relates to PMN apoptosi s, We found that Mcl-1 localized to the nucleus and cytoplasm and that expr ession levels decreased as PMN were aged in culture. Reducing available Mcl -1 through the nse of antisense oligonucleotides demonstrated that Mcl-1 is necessary to delay apoptosis during normal PMN aging and hypoxia but is no t required for suppression of apoptosis by laminin adhesion. Our results de monstrate a distinct expression pattern of Mcl-1 surd that Mcl-1 is crucial for the delay of apoptosis initiated by certain antiapoptotic factors.