Expression and differential regulation of natriuretic peptides in mouse macrophages.
The coexpression of the natriuretic peptides ANP, BNP and CNP as well as their differential regulation in mouse macrophages was demonstrated by quantitative PCR, HPLC analysis, and specific radioimmunoassays. Exposure of peritoneal- and bone marrow-derived macrophages to various immunomodulators revealed that bacterial LPS strikingly increases (up to 300-fold) the mRNA coding for CNP as does zymosan (up to 15-fold). In this respect, neither the phorbol ester PMA nor the glucocorticoid dexamethasone had any effect. Examination of macrophages for ANP mRNA showed a similar response to LPS and zymosan, though only a three- to sixfold increase, confirming previous data. In contrast, the concentration of mRNA coding for brain natriuretic peptide in these cells was reduced by dexamethasone (up to twofold) as well as LPS (two- to fivefold). No change was observed upon challenge with zymosan or PMA. The findings at the mRNA level are complemented by their corresponding peptide products. Incubation of macrophages with LPS resulted in a two- and fivefold elevation of intracellular ANP and CNP immunoreactivity, respectively. The amount of peptides released from cells under these conditions was found increased for ANP (threefold) and CNP (10-fold). No changes were observed for both intra- and extracellular brain natriuretic peptide. The coexpression of natriuretic peptides in macrophages as well as their different regulations by immunomodulators suggest discrete functions of these peptides within the immune system.
Vollmar
A M
AM
Institute of Pharmacology, Toxicology and Pharmacy, University of Munich, Germany.
Schulz
R
R
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001483:Base Sequence; D001854:Bone Marrow Cells; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017931:DNA Primers; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D011506:Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor