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Recombinant human granulocytemacrophage colony-stimulating factor induces granule exocytosis from human polymorphonuclear neutrophils

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Abstract

Exposure of human polymorphonuclear neutrophils (PMNs) to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in a time- and concentration-dependent (3–100 units/ml) extracellular release of a specific (vitamin B12-binding protein) but not azurophil granule constituent (myeloperoxidase). Negligible granule exocytosis occurred if PMNs were not preincubated with cytochalasin B prior to contact with GM-CSF. The extent of degranulation elicited with GM-CSF was reduced but not abolished when PMNs were incubated with EGTA in calcium-free medium. GM-CSF did not stimulate a rise in the cytosolic-free calcium concentration ([Ca2+],), and it had no effect on PMN protein kinase C (PKC) activity.

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References

  1. Clark, S. C., andR. Kamen. 1987. The human hematopoietic colony-stimulating factors.Science 236:1229–1237.

    Google Scholar 

  2. Weisbart, R. H., D. W. Golde, S. C. Clark, G. G. Wong, andJ. C. Gasson. 1985. Human granulocyte-macrophage colony-stimulating factor is a neutrophil activator.Nature 314:361–363.

    Google Scholar 

  3. Weisbart, R. H., L. Kwan, D. W. Golde, andJ. C, Gasson. 1987. Human GM-CSF primes neutrophils for enhanced oxidative metabolism in response to the major physiological chemoattractants.Blood 69:18–21.

    Google Scholar 

  4. Lopez, A. F., J. Williamson, J. R. Gamble, C. G. Begley, J. M. Harlan, S. J. Klebanoff, A. Waltersdorph, G. Wong, S. C. Clark, andM. A. Vadas. 1986. Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival.J. Clin. Invest. 78:1220–1228.

    Google Scholar 

  5. Dahinden, C. A., J. Zingg, F. E. Maly, andA. L. Deweck. 1988. Leukotriene production in human neutrophils primed by recombinant human granulocyte/macrophage colony-stimulating factor and stimulated with the complement component C5a and FMLP as second signals.J. Exp. Med. 167:1281–1295.

    Google Scholar 

  6. DiPersio, J. F., P. Billing, R. Williams, andJ. C. Gassson. 1988. Human granulocytemacrophage colony-stimulating factor and other cytokines prime human neutrophils for enhanced arachidonic acid release and leukotriene B4 synthesis.J. Immunol. 140:4315–4322.

    Google Scholar 

  7. Wirthmueller, U., A. Deweck, andC. A. Dahinden. 1989. Platelet-activating factor production in human neutrophils by sequential stimulation with granulocyte-macrophage colonystimulating factor and the chemotactic factors C5a or formyl-methionyl-leucyl-phenylalanine.J. Immunol. 142:3213–3218.

    Google Scholar 

  8. Gasson, J. C., S. E. Kaufman, R. H. Weisbart, M. Tomonaga, andD. E. Golde. 1986. High-affinity binding of granulocyte-macrophage colony-stimulating factor to normal and leukemic human myeloid cells.Proc. Natl. Acad. Sci. U.S.A. 83:669–673.

    Google Scholar 

  9. DiPersio, J., P. Billing, S. Kaufman, P. Echtesady, R. E. Williams, andJ. C. Gasson. 1988. Characterization of the human granulocyte-macrophage colony-stimulating factor receptor.J. Biol. Chem. 263:1834–1841.

    Google Scholar 

  10. Smith, R. J., J. M. Justen, andL. M. Sam. 1988. Function and stimulus-specific effects of phorbol 12-myristate 13-acetate on human polymorphonuclear neutrophils: Autoregulatory role for protein kinase C in signal transduction.Inflammation 12:597–611.

    Google Scholar 

  11. Henson, P. M., B. Zanolari, N. A. Schwartzman, andS. R. Hong. 1978. Intracellular control of human neutrophil secretion: 1. C5a-induced stimulus-specific desensitization and the effects of cytochalasin B.J. Immunol. 131:851–855.

    Google Scholar 

  12. Smith, R. J. 1978. Nonsteroid anti-inflammatory agents: Regulation of the phagocytic secretion of lysosomal enzymes from guinea-pig neutrophils.J. Pharmacol. Exp. Ther. 207:618–629.

    Google Scholar 

  13. Smith, R. J., W. Wierenga, andS. S. Iden. 1980. Characteristics of N-formyl-methionylleucyl-phenylalanine as an inducer of lysosomal enzyme release from human neutrophils.Inflammation 4:73–88.

    Google Scholar 

  14. Gottlieb, C., K. S. Lau, L. R. Wasserman, andV. Herbert. 1965. Rapid charcoal assay for intrinsic factor (IF), gastric juice unsaturated B12 binding capacity, antibody to IF, and serum unsaturated B12 binding capacity.Blood 25:875–884.

    Google Scholar 

  15. Bergmeyer, H. U., E. Bernt, andB. Hess. 1965. Lactic Dehydrogenase: Methods of Enzymatic Analysis. Verlag Chemie, Academic Press, New York. 736–743.

    Google Scholar 

  16. Sullivan, R., J. D. Griffin, E. R. Simons, A. I. Schafer, T. Meshulam, J. P. Fredette, A. K. Maas, A. S. Gadenne, J. L. Leavitt, andD. A. Melnick. 1987. Effects of recombinant human granulocyte and macrophage colony-stimulating factors on signal transduction pathways in human granulocytes.J. Immunol. 139:3422–3430.

    Google Scholar 

  17. Richter, J., T. Andersson, andI. Olsson. 1989. Effect of tumor necrosis factor and granulocyte/macrophage colony-stimulating factor on neutrpohil degranulation.J. Immunol. 142:3199–3205.

    Google Scholar 

  18. Costagna, M., Y. Takai, K. Kaibuchi, K. Sano, U. Kikkawa, andY. Nishizuka. 1982. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.J. Biol. Chem. 257:7847–7851.

    Google Scholar 

  19. West, B. C., A. S. Rosenthal, N. A. Gelb, andH. R. Kimball. 1974. Separation and characterization of human neutrophil granules.Am. J. Pathol. 77:41–66.

    Google Scholar 

  20. Wright, D. G., andJ. I. Gallin. 1977. The differential mobilization of human neutrophil granules: Effects of phorbol myristate acetate and ionophore A23187.Am. J. Pathol. 87:273–284.

    Google Scholar 

  21. Dewald, B., U. Bretz, andM. Baggiolini. 1982. Release of gelatinase from a novel secretory compartment of human neutrophils.J. Clin. Invest. 70:518–525.

    Google Scholar 

  22. Lew, D. P., A. Monod, F. A. Waldvogel, B. Dewald, M. Baggiolini, andT. Pozzan. 1986. Quantitative analysis of the cytosolic free calcium dependency of exocytosis from three subcellular compartments in intact human neutrophils.J. Cell. Biol. 102:2197–2204.

    Google Scholar 

  23. Weisbart, R., D. W. Golde, andJ. C. Gasson. 1986. Biosynthetic human GM-CSF modulates the number and affinity of neutrophil f-met-leu-phe receptors.J. Immunol. 137:3584–3587.

    Google Scholar 

  24. Socinski, M. A., S. A. Cannistra, R. Sullivan, A. Elias, K. Antman, L. Schnipper, andJ. D. Griffin. 1988. Granulocyte-macrophage colony-stimulating factor induces the expression of the CD11b surface adhesion molecule on human granulocytes in vivo.Blood 72:691–697.

    Google Scholar 

  25. Fletcher, M. P., andJ. I. Gallin. 1983. Human neutrophils contain an intracellular pool of putative reeptors for the chemoattractant N-formyl-methionyl-leucyl-phenylalanine.Blood 62:792–799.

    Google Scholar 

  26. Bainton, D. F., L. J. Miller, T. K. Kishimoto, andT. A. Springer. 1987. Leukocyte adhesion receptors are stored in peroxidase-negative granules of human neutrophils.J. Exp. Med. 166:1641–1653.

    Google Scholar 

  27. Dewald, B., andM. Baggiolini. 1986. Platelet-activating factor as a stimulus of exocytosis in human neutrophils.Biochim. Biophys. Acta 888:42–48.

    Google Scholar 

  28. Smith, R. J., B. J. Bowman, andS. S. Iden. 1983. Characteristics of 1-O-hexadecyl and 1-O-octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine-stimulated granule enzyme release from human neutrophils.Clin. Immunol. Immunopathol,28:13–28.

    Google Scholar 

  29. Smith, R. J., S. S. Iden, andB. J. Bowman. 1984. Activation of the human neutrophil secretory process with 5(S), 12(.R)-dihydroxy-6,14-cis-8,10-fran,s-eicosatetraenoic acid.Inflammation 8:365–384.

    Google Scholar 

  30. Bentwood, B. J., andP. M. Henson. 1980. C5a-induced degranulation from human neutrophils in the absence of cytochalasin B.Fed. Proc. 39:798.

    Google Scholar 

  31. Wessells, N. K., D. S. Spooner, J. F. Ash, M. O. Bradley, M. A. Luduena, E. L. TayLor, J. T. Wrenn, andK. M. Yamada. 1971. Microfilaments in cellular and developmental processes.Science 171:135–143.

    Google Scholar 

  32. Korchak, H. M., L. E. Rutherford, andG. Weissmann. 1984. Stimulus response coupling in the human neutrophil: 1. Kinetic analysis of changes in calcium permeabilityJ. Biol. Chem. 259:4070–4075.

    Google Scholar 

  33. Bradford, P. G., andR. P. Rubin. 1985. Characterization of formylmethionyl-leucylphenylalanine stimulation of inositol trisphosphate accumulation in rabbit neutrophils.Mol. Pharmacol. 27:74–78.

    Google Scholar 

  34. Honeycutt, P. J., andJ. E. Niedel. 1986. Cytochalasin B enhancement of the diacylglycerol response in formyl peptide-stimulated neutrophils.J. Biol. Chem. 261:15900–15905.

    Google Scholar 

  35. McColl, S.R., C. Kreis, J. F. DiPersio, P. Borgeat, andP. H. Naccache. 1989. Involvement of guanine nucleotide binding proteins in neutrophil activation and priming by GM-CSF.Blood 72:588–591.

    Google Scholar 

  36. Verghese, M. W., L. Charles, L. Jakoi, S. B. Dillon, andR. Snyderman. 1987. Role of a guanine nucleotide regulatory protein in the activation of phospholipase C by different chemoattractants.J. Immunol. 138:4374–4380.

    Google Scholar 

  37. Berridge, M. J. 1987. Inositol trisphosphate and diacylglycerol: Two interacting second messengers.Annu. Rev. Biochem. 56:159–193.

    Google Scholar 

  38. Nishizuka, Y. 1984. The role of protein kinase C in cell surface signal transduction and tumor promotion.Nature 308:693–698.

    Google Scholar 

  39. Berridge, M. J., andR. F. Irvin. 1984. Inositol trisphosphate, a novel second messenger, in cellular signal transduction.Nature 312:315–321.

    Google Scholar 

  40. Coffey, R. G., J. S. Davis, andJ. Y. Djeu. 1988. Stimulation of guanylate cyclase activity and reduction of adenylate cyclase activity by granulocyte-macrophage colony-stimulating factor in human blood neutrophils.J. Immunol. 140:2695–2701.

    Google Scholar 

  41. Zurier, R. B., G. Weissmann, S. Hoffstein, S. Kammerman, andH. H. Tai. 1974. Mechanisms of lysosomal enzyme release from human leukocytes: II. Effects of cAMP and GMP, autonomic agonists, and agents which affect microtubule function.J. Clin. Invest. 53:297–309.

    Google Scholar 

  42. Ignarro, L. J., T. F. Lint, andW. J. George. 1974. Hormonal control of lysosomal enzyme release from human neutrophils: Effects of autonomic neurohormones on enzyme release, phagocytosis, and cyclic nucleotide levels.J. Exp. Med. 139:1395–1414.

    Google Scholar 

  43. Nakazawa, K., andM. Sano. 1974. Studies on guanylate cyclase: A new assay method for guanylate cyclase and properties of the cyclase from rat brain.J. Biol. Chem. 249:4207–4211.

    Google Scholar 

  44. O'flaherty, J. T. 1985. Neutrophil degranulation: Evidence pertaining to its mediation by the combined effects of leukotriene B4, platelet-activating factor, and 5-HETE.J. Cell. Physiol. 122:229–239.

    Google Scholar 

  45. Firestein, G. S., R. Taetle, K. Kaushansky, andN. J. Zvaifler. 1989. Cytokines in chronic inflammatory arthritis. 2. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions.J. Clin. Invest. 83:876–882.

    Google Scholar 

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Smith, R.J., Justen, J.M. & Sam, L.M. Recombinant human granulocytemacrophage colony-stimulating factor induces granule exocytosis from human polymorphonuclear neutrophils. Inflammation 14, 83–92 (1990). https://doi.org/10.1007/BF00914032

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