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. 1993 Nov 1;295(Pt 3):679–684. doi: 10.1042/bj2950679

Characterization of a complement-fragment-C5a-stimulated calcium-influx mechanism in U937 monocytic cells.

P N Monk 1, L J Partridge 1
PMCID: PMC1134613  PMID: 8240277

Abstract

The mechanism by which complement fragment C5a elevates intracellular Ca2+ ([Ca2+]i) levels in two cell types, a monocytic cell line, U937, and neutrophils, has been investigated by the use of fluorometric and radiometric techniques. In U937 cells the influx of extracellular Ca2+ can be distinguished from the release of intracellular Ca2+ stores in terms of dose-responsiveness to C5a and sensitivity to pertussis-toxin poisoning. This suggests that the mechanism of Ca2+ influx in these cells is at least partially independent of both the production of inositol phosphates and elevation of internal Ca2+ concentration. The C5a-stimulated influx of 45Ca2+ into U937 cells is inhibited by a series of metal ions (Zn2+ > Co2+ > Mn2+ > Sr2+ approximately equal to Ni2+ > La3+). The stimulated influx of Ca2+ into neutrophils is inhibited differently (Ni2 >> Co2+ > Zn2+ approximately equal to La3+ > Mn2+ approximately equal to Sr2+), is less sensitive to C5a and both the influx of extracellular Ca2+ and the release of intracellular stores are equally sensitive to pertussis toxin treatment. Taken together these results indicate that [Ca2+]i is controlled in U937 monocytes by mechanisms distinct from those which appear to operate in other myeloid cells, such as neutrophils, stimulated with C5a and formylpeptide.

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Selected References

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  1. Alonso-Torre S. R., Alvarez J., Montero M., Sanchez A., García-Sancho J. Control of Ca2+ entry into HL60 and U937 human leukaemia cells by the filling state of the intracellular Ca2+ stores. Biochem J. 1993 Feb 1;289(Pt 3):761–766. doi: 10.1042/bj2890761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amatruda T. T., 3rd, Steele D. A., Slepak V. Z., Simon M. I. G alpha 16, a G protein alpha subunit specifically expressed in hematopoietic cells. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5587–5591. doi: 10.1073/pnas.88.13.5587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Banks P., Barker M. D., Burton D. R. Recruitment of actin to the cytoskeletons of human monocyte-like cells activated by complement fragment C5a. Is protein kinase C involved? Biochem J. 1988 Jun 15;252(3):765–769. doi: 10.1042/bj2520765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barnett Foster D. E., Dorrington K. J., Painter R. H. Structure and function of immunoglobulin domains. VII. Studies on the structural requirements of human immunoglobulin G for granulocyte binding. J Immunol. 1978 Jun;120(6):1952–1956. [PubMed] [Google Scholar]
  5. Boucek M. M., Snyderman R. Calcium influx requirement for human neutrophil chemotaxis: inhibition by lanthanum chloride. Science. 1976 Sep 3;193(4256):905–907. doi: 10.1126/science.948752. [DOI] [PubMed] [Google Scholar]
  6. Buhl A. M., Eisfelder B. J., Worthen G. S., Johnson G. L., Russell M. Selective coupling of the human anaphylatoxin C5a receptor and alpha 16 in human kidney 293 cells. FEBS Lett. 1993 May 24;323(1-2):132–134. doi: 10.1016/0014-5793(93)81464-b. [DOI] [PubMed] [Google Scholar]
  7. Davies E. V., Campbell A. K., Hallett M. B. Dissociation of store release from transmembrane influx of calcium in human neutrophils. FEBS Lett. 1992 Nov 23;313(2):121–125. doi: 10.1016/0014-5793(92)81426-m. [DOI] [PubMed] [Google Scholar]
  8. Goldman D. W., Chang F. H., Gifford L. A., Goetzl E. J., Bourne H. R. Pertussis toxin inhibition of chemotactic factor-induced calcium mobilization and function in human polymorphonuclear leukocytes. J Exp Med. 1985 Jul 1;162(1):145–156. doi: 10.1084/jem.162.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  10. Krautwurst D., Seifert R., Hescheler J., Schultz G. Formyl peptides and ATP stimulate Ca2+ and Na+ inward currents through non-selective cation channels via G-proteins in dibutyryl cyclic AMP-differentiated HL-60 cells. Involvement of Ca2+ and Na+ in the activation of beta-glucuronidase release and superoxide production. Biochem J. 1992 Dec 15;288(Pt 3):1025–1035. doi: 10.1042/bj2881025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lund-Johansen F., Olweus J. Signal transduction in monocytes and granulocytes measured by multiparameter flow cytometry. Cytometry. 1992;13(7):693–702. doi: 10.1002/cyto.990130705. [DOI] [PubMed] [Google Scholar]
  12. Merritt J. E., Greener M., Hallam T. J., Swayne G. T. The involvement of calcium and protein kinase C in modulating agonist-stimulated chemotaxis of human neutrophils. Cell Signal. 1991;3(1):73–77. doi: 10.1016/0898-6568(91)90010-r. [DOI] [PubMed] [Google Scholar]
  13. Monk P. N., Banks P. Evidence for the involvement of multiple signalling pathways in C5a-induced actin polymerization and nucleation in human monocyte-like cells. J Mol Endocrinol. 1991 Jun;6(3):241–247. doi: 10.1677/jme.0.0060241. [DOI] [PubMed] [Google Scholar]
  14. Monk P. N., Banks P. The role of protein kinase C activation and inositol phosphate production in the regulation of cell-surface expression of Mac-1 by complement fragment C5a. Biochim Biophys Acta. 1991 Apr 17;1092(2):251–255. doi: 10.1016/0167-4889(91)90164-s. [DOI] [PubMed] [Google Scholar]
  15. Omann G. M., Harter J. M., Hassan N., Mansfield P. J., Suchard S. J., Neubig R. R. A threshold level of coupled G-proteins is required to transduce neutrophil responses. J Immunol. 1992 Sep 15;149(6):2172–2178. [PubMed] [Google Scholar]
  16. Omann G. M., Porasik-Lowes M. M. Graded G-protein uncoupling by pertussis toxin treatment of human polymorphonuclear leukocytes. J Immunol. 1991 Feb 15;146(4):1303–1308. [PubMed] [Google Scholar]
  17. Pollock K., Creba J. Leukotriene D4 induced calcium changes in U937 cells may utilize mechanisms additional to inositol phosphate production that are pertussis toxin insensitive but are blocked by phorbol myristate acetate. Cell Signal. 1990;2(6):563–568. doi: 10.1016/0898-6568(90)90078-o. [DOI] [PubMed] [Google Scholar]
  18. Pollock K., Creba J., Mitchell F., Milligan G. Stimulus-response coupling in FMLP-stimulated U937 monocytes: effect of differentiation on Gi2 expression. Biochim Biophys Acta. 1990 Jan 23;1051(1):71–77. doi: 10.1016/0167-4889(90)90175-d. [DOI] [PubMed] [Google Scholar]
  19. Putney J. W., Jr Capacitative calcium entry revisited. Cell Calcium. 1990 Nov-Dec;11(10):611–624. doi: 10.1016/0143-4160(90)90016-n. [DOI] [PubMed] [Google Scholar]
  20. Saussy D. L., Jr, Sarau H. M., Foley J. J., Mong S., Crooke S. T. Mechanisms of leukotriene E4 partial agonist activity at leukotriene D4 receptors in differentiated U-937 cells. J Biol Chem. 1989 Nov 25;264(33):19845–19855. [PubMed] [Google Scholar]
  21. Schumann M. A., Tanigaki T., Heller D. N., Raffin T. A. Ca(2+)-dependent and Ca(2+)-independent mechanisms modulate whole-cell cationic currents in human neutrophils. Biochem Biophys Res Commun. 1992 Jun 15;185(2):531–538. doi: 10.1016/0006-291x(92)91657-c. [DOI] [PubMed] [Google Scholar]
  22. Sheth B., Banks P., Burton D. R., Monk P. N. The regulation of actin polymerization in differentiating U937 cells correlates with increased membrane levels of the pertussis-toxin-sensitive G-protein Gi2. Biochem J. 1991 May 1;275(Pt 3):809–811. doi: 10.1042/bj2750809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Simchowitz L., Cragoe E. J., Jr Polyvalent cations inhibit human neutrophil chemotaxis by interfering with the polymerization of actin. J Biol Chem. 1990 Aug 15;265(23):13457–13463. [PubMed] [Google Scholar]
  24. Simchowitz L., Foy M. A., Cragoe E. J., Jr A role for Na+/Ca2+ exchange in the generation of superoxide radicals by human neutrophils. J Biol Chem. 1990 Aug 15;265(23):13449–13456. [PubMed] [Google Scholar]
  25. von Tscharner V., Prod'hom B., Baggiolini M., Reuter H. Ion channels in human neutrophils activated by a rise in free cytosolic calcium concentration. 1986 Nov 27-Dec 3Nature. 324(6095):369–372. doi: 10.1038/324369a0. [DOI] [PubMed] [Google Scholar]

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