Journal
JOURNAL OF IMMUNOLOGY
Volume 173, Issue 1, Pages 123-135Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.173.1.123
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Funding
- NCRR NIH HHS [RR 00059] Funding Source: Medline
- NHLBI NIH HHS [HL 71040, HL 68135, HL 60316, HL 55584] Funding Source: Medline
- NIEHS NIH HHS [ES 09607, ES 09204] Funding Source: Medline
- NIGMS NIH HHS [GM 067877] Funding Source: Medline
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Human alveolar macrophages are unique in that they have an extended life span in contrast to precursor monocytes. In evaluating the role of sphingolipids in alveolar macrophage survival, we found high levels of sphingosine, but not sphingosine-1-phosphate. Sphingosine is generated by the action of ceramidase(s) on ceramide, and alveolar macrophages have high constitutive levels of acid ceramidase mRNA, protein, and activity. The high levels of acid ceramidase were specific to alveolar macrophages, because there was little ceramidase protein or activity (or sphingosine) in monocytes from matching donors. In evaluating prolonged survival of alveolar macrophages, we observed a requirement for constitutive activity of ERK MAPK and the PI3K downstream effector Akt. Blocking acid ceramidase but not sphingosine kinase activity in alveolar macrophages led to decreased ERK and Akt activity and induction of cell death. These studies suggest an important role for sphingolipids in prolonging survival of human alveolar macrophages via distinct survival pathways.
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