The loss of Mcl-1 expression in human polymorphonuclear leukocytes promotes apoptosis.
The regulation of polymorphonuclear leukocyte (PMN) apoptosis can influence the duration of the inflammatory response. We have previously shown that PMN apoptosis is delayed by matrix adhesion and hypoxia; however, the mechanisms responsible for this delay are not well understood. Mcl-1, an antiapoptotic Bcl-2 family member, is present in neutrophils; therefore, we sought to characterize its localization and function as it relates to PMN apoptosis. We found that Mcl-1 localized to the nucleus and cytoplasm and that expression levels decreased as PMN were aged in culture. Reducing available Mcl-1 through the use of antisense oligonucleotides demonstrated that Mcl-1 is necessary to delay apoptosis during normal PMN aging and hypoxia but is not required for suppression of apoptosis by laminin adhesion. Our results demonstrate a distinct expression pattern of Mcl-1 and that Mcl-1 is crucial for the delay of apoptosis initiated by certain antiapoptotic factors.
Brown University School of Medicine and Rhode Island Hospital, Division of Surgical Research, Providence 02903, USA.
S J
SJ
Leuenroth
P S
PS
Grutkoski
A
A
Ayala
H H
HH
Simms
D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D015687:Cell Hypoxia; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2; D012128:Respiratory Distress Syndrome / Q000473:pathology
D007797:Laminin; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2