Interleukin-1 increases vacuolar-type H +-ATPase activity in murine peritoneal macrophages

Guy F. Brisseau, Sergio Grinstein, David Hackam, Tommy Nordström, Morris F. Manolson, Aye Aye Khine, Ori D. Rotstein

Research output: Contribution to journalArticle

Abstract

Maintenance of cytoplasmic pH (pH(i)) within a narrow physiological range is crucial to normal cellular function. This is of particular relevance to phagocytic cells within the acidic inflammatory microenvironment where the pHi tends to be acid loaded. We have previously reported that a vacuolar- type H +-ATPase (V-ATPase) situated in the plasma membrane of macrophages and poised to extrude protons from the cytoplasmic to the extracellular space is an important pH(i) regulatory mechanism within the inflammatory milieu. Since this microenvironment is frequently characterized by the influx of cells known to release inflammatory cytokines, we performed studies to examine the effect of one such mediator molecule, interleukin-1 (IL-1), on pH(i) regulation in peritoneal macrophages. IL-1 caused a time- and dose-dependent increase in macrophage pH(i) recovery from an acute acid load. This effect was specific to IL-1 and was due to enhanced plasmalemmal V-ATPase activity. The increased V-ATPase activity by IL-1 occurred following a lag period of several hours and required de novo protein and mRNA synthesis. However, Northern blot analysis revealed that IL-1 did not exert its effect via alterations in the levels of mRNA transcripts for the A or B subunits of the V-ATPase complex. Finally, stimulation of both cAMP-dependent protein kinase and protein kinase C was required for the stimulatory effect of IL-1 on V- ATPase activity. Thus, cytokines present within the inflammatory milieu are able to modulate pHi regulatory mechanisms. These data may represent a novel mechanism whereby cytokines may improve cellular function at inflammatory sites.

Original languageEnglish (US)
Pages (from-to)2005-2011
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number4
DOIs
StatePublished - Jan 26 1996
Externally publishedYes

Fingerprint

Vacuolar Proton-Translocating ATPases
Macrophages
Peritoneal Macrophages
Interleukin-1
Cytokines
Messenger RNA
Acids
Proton-Translocating ATPases
Extracellular Space
Cell membranes
Phagocytes
Cyclic AMP-Dependent Protein Kinases
Northern Blotting
Protein Kinase C
Adenosine Triphosphatases
Protons
Maintenance
Cell Membrane
Recovery
Molecules

ASJC Scopus subject areas

  • Biochemistry

Cite this

Brisseau, G. F., Grinstein, S., Hackam, D., Nordström, T., Manolson, M. F., Khine, A. A., & Rotstein, O. D. (1996). Interleukin-1 increases vacuolar-type H +-ATPase activity in murine peritoneal macrophages. Journal of Biological Chemistry, 271(4), 2005-2011. https://doi.org/10.1074/jbc.271.4.2005

Interleukin-1 increases vacuolar-type H +-ATPase activity in murine peritoneal macrophages. / Brisseau, Guy F.; Grinstein, Sergio; Hackam, David; Nordström, Tommy; Manolson, Morris F.; Khine, Aye Aye; Rotstein, Ori D.

In: Journal of Biological Chemistry, Vol. 271, No. 4, 26.01.1996, p. 2005-2011.

Research output: Contribution to journalArticle

Brisseau, GF, Grinstein, S, Hackam, D, Nordström, T, Manolson, MF, Khine, AA & Rotstein, OD 1996, 'Interleukin-1 increases vacuolar-type H +-ATPase activity in murine peritoneal macrophages', Journal of Biological Chemistry, vol. 271, no. 4, pp. 2005-2011. https://doi.org/10.1074/jbc.271.4.2005
Brisseau, Guy F. ; Grinstein, Sergio ; Hackam, David ; Nordström, Tommy ; Manolson, Morris F. ; Khine, Aye Aye ; Rotstein, Ori D. / Interleukin-1 increases vacuolar-type H +-ATPase activity in murine peritoneal macrophages. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 4. pp. 2005-2011.
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