Polyphosphate is a Novel Pro-inflammatory Regulator of Mast Cells and is Located in Acidocalcisomes

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 Jul 5

PMID 22761438

Citations 78

Authors

David Moreno-Sanchez

Laura Hernandez-Ruiz

Felix A Ruiz

Roberto Docampo

Affiliations

Soon will be listed here.

Abstract

Polyphosphate (polyP) is a pro-inflammatory agent and a potent modulator of the human blood-clotting system. The presence of polyP of 60 phosphate units was identified in rat basophilic leukemia (RBL-2H3) mast cells using specific enzymatic assays, urea-polyacrylamide gel electrophoresis of cell extracts, and staining of cells with 4,6-diamidino-2-phenylindole (DAPI), and the polyP-binding domain of Escherichia coli exopolyphosphatase. PolyP co-localizes with serotonin- but not with histamine-containing granules. PolyP levels greatly decreased in mast cells stimulated to degranulate by IgE. Mast cell granules were isolated and found to be acidic and decrease their polyP content upon alkalinization. In agreement with these results, when RBL-2H3 mast cells were loaded with the fluorescent calcium indicator fura-2 acetoxymethyl ester to measure their intracellular Ca(2+) concentration ([Ca(2+)](i)), they were shown to possess a significant amount of Ca(2+) stored in an acidic compartment different from lysosomes. PolyP derived from RBL-2H3 mast cells stimulated bradykinin formation, and it was also detected in human basophils. All of these characteristics of mast cell granules, together with their known elemental composition, and high density, are similar to those of acidocalcisomes. The results suggest that mast cells polyP could be an important mediator of their pro-inflammatory and pro-coagulant activities.

Citing Articles

Elevated basophils in peripheral blood predict lower extremity deep venous thrombosis in non-surgical patients with spontaneous intracerebral hemorrhage.

Liu C, Wu B, Luo L, Wang J, Hu W, Zhang X Sci Rep. 2025; 15(1):7397.

PMID: 40032934 PMC: 11876693. DOI: 10.1038/s41598-025-91851-x.

ESIPT fluorescence turn-on sensors for detection of short chain inorganic polyphosphate in water.

Roy S, Moser S, Durr-Mayer T, Hinkelmann R, Jessen H Org Biomol Chem. 2024; 23(6):1373-1379.

PMID: 39714782 PMC: 11665774. DOI: 10.1039/d4ob01926a.

Inorganic Polyphosphate Promotes Colorectal Cancer Growth via TRPM8 Receptor Signaling Pathway.

Arre V, Balestra F, Scialpi R, Dituri F, Donghia R, Coletta S Cancers (Basel). 2024; 16(19).

PMID: 39409946 PMC: 11476407. DOI: 10.3390/cancers16193326.

Inorganic Polyphosphate Is in the Surface of but Is Not Significantly Secreted.

Crowe L, Gioseffi A, Bertolini M, Docampo R Pathogens. 2024; 13(9).

PMID: 39338967 PMC: 11434814. DOI: 10.3390/pathogens13090776.

Antipolyphosphate monoclonal antibodies derived from autoimmune mice.

Sedzro J, Smith S, Scott A, Wang Y, Travers R, Hemp R Res Pract Thromb Haemost. 2024; 8(6):102550.

PMID: 39309228 PMC: 11414566. DOI: 10.1016/j.rpth.2024.102550.

References

Ramos I, Gomes F, Koeller C, Saito K, Heise N, Masuda H . Acidocalcisomes as calcium- and polyphosphate-storage compartments during embryogenesis of the insect Rhodnius prolixus Stahl. PLoS One. 2011; 6(11):e27276. PMC: 3214050. DOI: 10.1371/journal.pone.0027276. View

Smith S, Morrissey J . Polyphosphate enhances fibrin clot structure. Blood. 2008; 112(7):2810-6. PMC: 2556616. DOI: 10.1182/blood-2008-03-145755. View

Foster M, Leapman R, Li M, Atwater I . Elemental composition of secretory granules in pancreatic islets of Langerhans. Biophys J. 1993; 64(2):525-32. PMC: 1262355. DOI: 10.1016/S0006-3495(93)81397-3. View

Kovanen P . Mast cells in atherogenesis: actions and reactions. Curr Atheroscler Rep. 2009; 11(3):214-9. DOI: 10.1007/s11883-009-0033-7. View

Rao N, Gomez-Garcia M, Kornberg A . Inorganic polyphosphate: essential for growth and survival. Annu Rev Biochem. 2009; 78:605-47. DOI: 10.1146/annurev.biochem.77.083007.093039. View

Prussin C, Metcalfe D . 4. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol. 2003; 111(2 Suppl):S486-94. DOI: 10.1067/mai.2003.120. View

Chodaczek G, Bacsi A, Dharajiya N, Sur S, Hazra T, Boldogh I . Ragweed pollen-mediated IgE-independent release of biogenic amines from mast cells via induction of mitochondrial dysfunction. Mol Immunol. 2009; 46(13):2505-14. PMC: 2713802. DOI: 10.1016/j.molimm.2009.05.023. View

Smith S, Mutch N, Baskar D, Rohloff P, Docampo R, Morrissey J . Polyphosphate modulates blood coagulation and fibrinolysis. Proc Natl Acad Sci U S A. 2006; 103(4):903-8. PMC: 1347979. DOI: 10.1073/pnas.0507195103. View

Medina F, Segundo C, Campos-Caro A, Gonzalez-Garcia I, Brieva J . The heterogeneity shown by human plasma cells from tonsil, blood, and bone marrow reveals graded stages of increasing maturity, but local profiles of adhesion molecule expression. Blood. 2002; 99(6):2154-61. DOI: 10.1182/blood.v99.6.2154. View

10.

Raison S, Gillot I, Choine C, Pistone P, Pagnotta S, Laugier J . Ca increase in secretory granules of stimulated mast cells. Cell Calcium. 1999; 26(3-4):111-9. DOI: 10.1054/ceca.1999.0062. View

11.

Kendall M, Warley A . Elemental content of mast cell granules measured by X-ray microanalysis of rat thymic tissue sections. J Cell Sci. 1986; 83:77-87. DOI: 10.1242/jcs.83.1.77. View

12.

Smith S, Morrissey J . Sensitive fluorescence detection of polyphosphate in polyacrylamide gels using 4',6-diamidino-2-phenylindol. Electrophoresis. 2007; 28(19):3461-5. DOI: 10.1002/elps.200700041. View

13.

Teshima R, Amano F, Nakamura R, Tanaka Y, Sawada J . Effects of polyunsaturated fatty acids on calcium response and degranulation from RBL-2H3 cells. Int Immunopharmacol. 2006; 7(2):205-10. DOI: 10.1016/j.intimp.2006.09.017. View

14.

Kanerva K, Lappalainen J, Makitie L, Virolainen S, Kovanen P, Andersson L . Expression of antizyme inhibitor 2 in mast cells and role of polyamines as selective regulators of serotonin secretion. PLoS One. 2009; 4(8):e6858. PMC: 2730566. DOI: 10.1371/journal.pone.0006858. View

15.

Thastrup O, Cullen P, Drobak B, Hanley M, Dawson A . Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc Natl Acad Sci U S A. 1990; 87(7):2466-70. PMC: 53710. DOI: 10.1073/pnas.87.7.2466. View

16.

Saito K, Ohtomo R, Kuga-Uetake Y, Aono T, Saito M . Direct labeling of polyphosphate at the ultrastructural level in Saccharomyces cerevisiae by using the affinity of the polyphosphate binding domain of Escherichia coli exopolyphosphatase. Appl Environ Microbiol. 2005; 71(10):5692-701. PMC: 1266008. DOI: 10.1128/AEM.71.10.5692-5701.2005. View

17.

Chakravarty N, Nielsen E . Ca2+-Mg2+-activated adenosine triphosphatase in plasma and granule membranes in non-secreting and secreting mast cells. Exp Cell Res. 1980; 130(1):175-84. DOI: 10.1016/0014-4827(80)90054-3. View

18.

Seufferheld M, Vieira M, Ruiz F, Rodrigues C, Moreno S, Docampo R . Identification of organelles in bacteria similar to acidocalcisomes of unicellular eukaryotes. J Biol Chem. 2003; 278(32):29971-8. DOI: 10.1074/jbc.M304548200. View

19.

Haller T, Dietl P, Deetjen P, Volkl H . The lysosomal compartment as intracellular calcium store in MDCK cells: a possible involvement in InsP3-mediated Ca2+ release. Cell Calcium. 1996; 19(2):157-65. DOI: 10.1016/s0143-4160(96)90084-6. View

20.

Ruiz F, Lea C, Oldfield E, Docampo R . Human platelet dense granules contain polyphosphate and are similar to acidocalcisomes of bacteria and unicellular eukaryotes. J Biol Chem. 2004; 279(43):44250-7. DOI: 10.1074/jbc.M406261200. View