Cooperative prosurvival activity by ERK and Akt in human alveolar macrophages is dependent on high levels of acid ceramidase activity

Martha M Monick; Rama K Mallampalli; Mary Bradford; Diann McCoy; Thomas J Gross; Dawn M Flaherty; Linda S Powers; Kelli Cameron; Samuel Kelly; Alfred H Merrill Jr; Gary W Hunninghake

doi:10.4049/jimmunol.173.1.123

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Cooperative prosurvival activity by ERK and Akt in human alveolar macrophages is dependent on high levels of acid ceramidase activity

Journal article

Peer reviewed

Cooperative prosurvival activity by ERK and Akt in human alveolar macrophages is dependent on high levels of acid ceramidase activity

Martha M Monick, Rama K Mallampalli, Mary Bradford, Diann McCoy, Thomas J Gross, Dawn M Flaherty, Linda S Powers, Kelli Cameron, Samuel Kelly, Alfred H Merrill Jr, …

The Journal of immunology (1950), Vol.173(1), pp.123-135

07/01/2004

DOI: 10.4049/jimmunol.173.1.123

PMID: 15210766

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Abstract

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.

Cell Survival

Protein-Serine-Threonine Kinases - physiology

Humans

Cells, Cultured

Galactosylgalactosylglucosylceramidase - genetics

Macrophages, Alveolar - physiology

RNA, Messenger - analysis

Galactosylgalactosylglucosylceramidase - physiology

Macrophages, Alveolar - chemistry

Proto-Oncogene Proteins c-akt

Sphingosine - pharmacology

Mitogen-Activated Protein Kinases - physiology

Proto-Oncogene Proteins - physiology

Sphingosine - analysis

Galactosylgalactosylglucosylceramidase - analysis

Protein Kinase C-delta

Details

Title: Subtitle: Cooperative prosurvival activity by ERK and Akt in human alveolar macrophages is dependent on high levels of acid ceramidase activity
Creators: Martha M Monick - Division of Pulmonary, Critical Care, and Occupational Medicine, Roy J. and Lucille A. Carver College of Medicine, Eckstein Medical Research Building Room 100, University of Iowa, Iowa City, IA 52242, USA. martha-monick@uiowa.edu
Rama K Mallampalli
Mary Bradford
Diann McCoy
Thomas J Gross
Dawn M Flaherty
Linda S Powers
Kelli Cameron
Samuel Kelly
Alfred H Merrill Jr
Gary W Hunninghake
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.173(1), pp.123-135
DOI: 10.4049/jimmunol.173.1.123
PMID: 15210766
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: HL 71040 / NHLBI NIH HHS ES 09204 / NIEHS NIH HHS GM 067877 / NIGMS NIH HHS HL 55584 / NHLBI NIH HHS ES 09607 / NIEHS NIH HHS HL 68135 / NHLBI NIH HHS HL 60316 / NHLBI NIH HHS RR 00059 / NCRR NIH HHS
Language: English
Date published: 07/01/2004
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984094584302771

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