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. 1995 Jun;95(6):2442–2450. doi: 10.1172/JCI117944

Expression and differential regulation of natriuretic peptides in mouse macrophages.

A M Vollmar 1, R Schulz 1
PMCID: PMC295918  PMID: 7769089

Abstract

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.

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  1. Adams D. O., Hamilton T. A. The cell biology of macrophage activation. Annu Rev Immunol. 1984;2:283–318. doi: 10.1146/annurev.iy.02.040184.001435. [DOI] [PubMed] [Google Scholar]
  2. Blalock J. E. A molecular basis for bidirectional communication between the immune and neuroendocrine systems. Physiol Rev. 1989 Jan;69(1):1–32. doi: 10.1152/physrev.1989.69.1.1. [DOI] [PubMed] [Google Scholar]
  3. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  4. Dagnino L., Lavigne J. P., Nemer M. Increased transcripts for B-type natriuretic peptide in spontaneously hypertensive rats. Quantitative polymerase chain reaction for atrial and brain natriuretic peptide transcripts. Hypertension. 1992 Nov;20(5):690–700. doi: 10.1161/01.hyp.20.5.690. [DOI] [PubMed] [Google Scholar]
  5. Furuya M., Yoshida M., Hayashi Y., Ohnuma N., Minamino N., Kangawa K., Matsuo H. C-type natriuretic peptide is a growth inhibitor of rat vascular smooth muscle cells. Biochem Biophys Res Commun. 1991 Jun 28;177(3):927–931. doi: 10.1016/0006-291x(91)90627-j. [DOI] [PubMed] [Google Scholar]
  6. Gerbes A. L., Dagnino L., Nguyen T., Nemer M. Transcription of brain natriuretic peptide and atrial natriuretic peptide genes in human tissues. J Clin Endocrinol Metab. 1994 Jun;78(6):1307–1311. doi: 10.1210/jcem.78.6.8200930. [DOI] [PubMed] [Google Scholar]
  7. Gessani S., Testa U., Varano B., Di Marzio P., Borghi P., Conti L., Barberi T., Tritarelli E., Martucci R., Seripa D. Enhanced production of LPS-induced cytokines during differentiation of human monocytes to macrophages. Role of LPS receptors. J Immunol. 1993 Oct 1;151(7):3758–3766. [PubMed] [Google Scholar]
  8. Gilliland G., Perrin S., Blanchard K., Bunn H. F. Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2725–2729. doi: 10.1073/pnas.87.7.2725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Green S. P., Hamilton J. A., Phillips W. A. Zymosan-triggered tyrosine phosphorylation in mouse bone-marrow-derived macrophages is enhanced by respiratory-burst priming agents. Biochem J. 1992 Dec 1;288(Pt 2):427–432. doi: 10.1042/bj2880427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gutkowska J., Nemer M. Structure, expression, and function of atrial natriuretic factor in extraatrial tissues. Endocr Rev. 1989 Nov;10(4):519–536. doi: 10.1210/edrv-10-4-519. [DOI] [PubMed] [Google Scholar]
  11. Han J. H., Beutler B., Huez G. Complex regulation of tumor necrosis factor mRNA turnover in lipopolysaccharide-activated macrophages. Biochim Biophys Acta. 1991 Aug 27;1090(1):22–28. doi: 10.1016/0167-4781(91)90032-h. [DOI] [PubMed] [Google Scholar]
  12. Hasegawa K., Fujiwara H., Itoh H., Nakao K., Fujiwara T., Imura H., Kawai C. Light and electron microscopic localization of brain natriuretic peptide in relation to atrial natriuretic peptide in porcine atrium. Immunohistocytochemical study using specific monoclonal antibodies. Circulation. 1991 Sep;84(3):1203–1209. doi: 10.1161/01.cir.84.3.1203. [DOI] [PubMed] [Google Scholar]
  13. Herman J. P., Langub M. C., Jr, Watson R. E., Jr Localization of C-type natriuretic peptide mRNA in rat hypothalamus. Endocrinology. 1993 Oct;133(4):1903–1906. doi: 10.1210/endo.133.4.8404633. [DOI] [PubMed] [Google Scholar]
  14. Hira G. K., Sarda I. R., Wong S. T., Pang S. C., Flynn T. G. Immunoactive iso-ANP/BNP in plasma, tissues and atrial granules of the rat. Regul Pept. 1993 Mar 5;44(1):1–9. doi: 10.1016/0167-0115(93)90124-q. [DOI] [PubMed] [Google Scholar]
  15. Ishizaka Y., Kangawa K., Minamino N., Ishii K., Takano S., Eto T., Matsuo H. Isolation and identification of C-type natriuretic peptide in human monocytic cell line, THP-1. Biochem Biophys Res Commun. 1992 Dec 15;189(2):697–704. doi: 10.1016/0006-291x(92)92257-x. [DOI] [PubMed] [Google Scholar]
  16. Jamison R. L., Canaan-Kühl S., Pratt R. The natriuretic peptides and their receptors. Am J Kidney Dis. 1992 Nov;20(5):519–530. doi: 10.1016/s0272-6386(12)70269-x. [DOI] [PubMed] [Google Scholar]
  17. Kelso A. Cytokines: structure, function and synthesis. Curr Opin Immunol. 1989 Dec;2(2):215–225. doi: 10.1016/0952-7915(89)90191-x. [DOI] [PubMed] [Google Scholar]
  18. Kojima M., Minamino N., Kangawa K., Matsuo H. Cloning and sequence analysis of a cDNA encoding a precursor for rat C-type natriuretic peptide (CNP). FEBS Lett. 1990 Dec 10;276(1-2):209–213. doi: 10.1016/0014-5793(90)80544-s. [DOI] [PubMed] [Google Scholar]
  19. Kolls J., Deininger P., Cohen J. C., Larson J. cDNA equalization for reverse transcription-polymerase chain reaction quantitation. Anal Biochem. 1993 Feb 1;208(2):264–269. doi: 10.1006/abio.1993.1044. [DOI] [PubMed] [Google Scholar]
  20. Krieger M., Acton S., Ashkenas J., Pearson A., Penman M., Resnick D. Molecular flypaper, host defense, and atherosclerosis. Structure, binding properties, and functions of macrophage scavenger receptors. J Biol Chem. 1993 Mar 5;268(7):4569–4572. [PubMed] [Google Scholar]
  21. Mattana J., Singhal P. C. Effects of atrial natriuretic peptide and cGMP on uptake of IgG complexes by macrophages. Am J Physiol. 1993 Jul;265(1 Pt 1):C92–C98. doi: 10.1152/ajpcell.1993.265.1.C92. [DOI] [PubMed] [Google Scholar]
  22. Moss R. B., Golightly M. G. In vitro enhancement of natural cytotoxicity by atrial natriuretic peptide fragment 4-28. Peptides. 1991 Jul-Aug;12(4):851–854. doi: 10.1016/0196-9781(91)90145-f. [DOI] [PubMed] [Google Scholar]
  23. Mäntymaa P., Vuolteenaho O., Marttila M., Ruskoaho H. Atrial stretch induces rapid increase in brain natriuretic peptide but not in atrial natriuretic peptide gene expression in vitro. Endocrinology. 1993 Sep;133(3):1470–1473. doi: 10.1210/endo.133.3.8365376. [DOI] [PubMed] [Google Scholar]
  24. Nakao K., Ogawa Y., Suga S., Imura H. Molecular biology and biochemistry of the natriuretic peptide system. I: Natriuretic peptides. J Hypertens. 1992 Sep;10(9):907–912. [PubMed] [Google Scholar]
  25. Nakao K., Ogawa Y., Suga S., Imura H. Molecular biology and biochemistry of the natriuretic peptide system. II: Natriuretic peptide receptors. J Hypertens. 1992 Oct;10(10):1111–1114. doi: 10.1097/00004872-199210000-00002. [DOI] [PubMed] [Google Scholar]
  26. Narumi S., Hamilton T. A. Inducible expression of murine IP-10 mRNA varies with the state of macrophage inflammatory activity. J Immunol. 1991 May 1;146(9):3038–3044. [PubMed] [Google Scholar]
  27. Parod R. J., Brain J. D. Uptake of latex particles by macrophages: characterization using flow cytometry. Am J Physiol. 1983 Sep;245(3):C220–C226. doi: 10.1152/ajpcell.1983.245.3.C220. [DOI] [PubMed] [Google Scholar]
  28. Peppel K., Vinci J. M., Baglioni C. The AU-rich sequences in the 3' untranslated region mediate the increased turnover of interferon mRNA induced by glucocorticoids. J Exp Med. 1991 Feb 1;173(2):349–355. doi: 10.1084/jem.173.2.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Porter J. G., Catalano R., McEnroe G., Lewicki J. A., Protter A. A. C-type natriuretic peptide inhibits growth factor-dependent DNA synthesis in smooth muscle cells. Am J Physiol. 1992 Nov;263(5 Pt 1):C1001–C1006. doi: 10.1152/ajpcell.1992.263.5.C1001. [DOI] [PubMed] [Google Scholar]
  30. Rosenzweig A., Seidman C. E. Atrial natriuretic factor and related peptide hormones. Annu Rev Biochem. 1991;60:229–255. doi: 10.1146/annurev.bi.60.070191.001305. [DOI] [PubMed] [Google Scholar]
  31. Seidman C. E., Bloch K. D., Klein K. A., Smith J. A., Seidman J. G. Nucleotide sequences of the human and mouse atrial natriuretic factor genes. Science. 1984 Dec 7;226(4679):1206–1209. doi: 10.1126/science.6542248. [DOI] [PubMed] [Google Scholar]
  32. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  33. Stanley E. R., Chen D. M., Lin H. S. Induction of macrophage production and proliferation by a purified colony stimulating factor. Nature. 1978 Jul 13;274(5667):168–170. doi: 10.1038/274168a0. [DOI] [PubMed] [Google Scholar]
  34. Steinhelper M. E. Structure, expression, and genomic mapping of the mouse natriuretic peptide type-B gene. Circ Res. 1993 May;72(5):984–992. doi: 10.1161/01.res.72.5.984. [DOI] [PubMed] [Google Scholar]
  35. Suga S., Itoh H., Komatsu Y., Ogawa Y., Hama N., Yoshimasa T., Nakao K. Cytokine-induced C-type natriuretic peptide (CNP) secretion from vascular endothelial cells--evidence for CNP as a novel autocrine/paracrine regulator from endothelial cells. Endocrinology. 1993 Dec;133(6):3038–3041. doi: 10.1210/endo.133.6.8243333. [DOI] [PubMed] [Google Scholar]
  36. Takahashi T., Allen P. D., Izumo S. Expression of A-, B-, and C-type natriuretic peptide genes in failing and developing human ventricles. Correlation with expression of the Ca(2+)-ATPase gene. Circ Res. 1992 Jul;71(1):9–17. doi: 10.1161/01.res.71.1.9. [DOI] [PubMed] [Google Scholar]
  37. Throsby M., Yang Z., Lee D., Huang W., Copolov D. L., Lim A. T. In vitro evidence for atrial natriuretic factor-(5-28) production by macrophages of adult rat thymi. Endocrinology. 1993 May;132(5):2184–2190. doi: 10.1210/endo.132.5.8477663. [DOI] [PubMed] [Google Scholar]
  38. Vollmar A. M., Colbatzky F., Schulz R. Expression of atrial natriuretic peptide in thymic macrophages after dexamethasone treatment of rats. Cell Tissue Res. 1992 May;268(2):397–399. doi: 10.1007/BF00318809. [DOI] [PubMed] [Google Scholar]
  39. Vollmar A. M., Colbatzky F., Schulz R. Increased production of atrial natriuretic peptide in the rat thymus after irradiation. Immunopharmacology. 1993 Jul-Aug;26(1):65–72. doi: 10.1016/0162-3109(93)90066-y. [DOI] [PubMed] [Google Scholar]
  40. Vollmar A. M., Gerbes A. L., Nemer M., Schulz R. Detection of C-type natriuretic peptide (CNP) transcript in the rat heart and immune organs. Endocrinology. 1993 Apr;132(4):1872–1874. doi: 10.1210/endo.132.4.8462485. [DOI] [PubMed] [Google Scholar]
  41. Vollmar A. M., Schulz R. Atrial natriuretic peptide is synthesized in the human thymus. Endocrinology. 1990 May;126(5):2277–2280. doi: 10.1210/endo-126-5-2277. [DOI] [PubMed] [Google Scholar]
  42. Vollmar A. M., Schulz R. Dexamethasone action on rat thymic atrial natriuretic peptide. Endocrinology. 1990 Dec;127(6):3240–3242. doi: 10.1210/endo-127-6-3240. [DOI] [PubMed] [Google Scholar]
  43. Vollmar A. M., Schulz R. Gene expression and secretion of atrial natriuretic peptide by murine macrophages. J Clin Invest. 1994 Aug;94(2):539–545. doi: 10.1172/JCI117367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wei C. M., Heublein D. M., Perrella M. A., Lerman A., Rodeheffer R. J., McGregor C. G., Edwards W. D., Schaff H. V., Burnett J. C., Jr Natriuretic peptide system in human heart failure. Circulation. 1993 Sep;88(3):1004–1009. doi: 10.1161/01.cir.88.3.1004. [DOI] [PubMed] [Google Scholar]
  45. Wiedermann C. J., Niedermühlbichler M., Braunsteiner H., Widermann C. J. Priming of polymorphonuclear neutrophils by atrial natriuretic peptide in vitro. J Clin Invest. 1992 May;89(5):1580–1586. doi: 10.1172/JCI115752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Yu S. F., Koerner T. J., Adams D. O. Gene regulation in macrophage activation: differential regulation of genes encoding for tumor necrosis factor, interleukin-1, JE, and KC by interferon-gamma and lipopolysaccharide. J Leukoc Biol. 1990 Nov;48(5):412–419. doi: 10.1002/jlb.48.5.412. [DOI] [PubMed] [Google Scholar]

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