Chemoattractant Receptors and Signal Transduction Processes

  • Ronald J. Uhing
  • Susan B. Dillon
  • Paul G. Polakis
  • Artis P. TruettIII
  • Ralph Snyderman
Part of the New Horizons in Therapeutics book series (NHTH)


Leukocyte responses to chemotactic and other phlogistic stimuli are vital for host defense and substantial interest has thus been focused on defining the mechanisms of signal transduction in these cells. Chemoattractants initiate leukocyte activation subsequent to binding to specific receptors on the cell surface. Temporal studies show that chemoattractants elicit rapid (≤5 s) increases in phosphoinositide metabolism and cytosolic calcium levels followed by changes in physiological function, for example, shape change, superoxide production, or degranulation. The ability of pharmacological agents (e.g., calcium ionophores or phorbol esters) to elicit similar functions suggests the central role of calcium mobilization, phosphoinositide metabolism, and protein kinase C in leukocyte activation. Although specific receptors are present for different classes of chemoattractants, they all appear to utilize a common mechanism for increasing cytosolic calcium. Chemoattractants also increase cellular cAMP levels, in this case by a calcium-mediated inhibition of cAMP degradation. This may serve an autoregulatory role in chemoattractant-induced leukocyte activation.


Human Neutrophil Respiratory Burst Pertussis Toxin Calcium Ionophore Calcium Mobilization 
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  1. Aksamit, R. R. Backlund, P. S., Jr., and Cantoni, G. L., 1985, Cholera toxin inhibits chemotaxis by a cAMP-independent mechanism, Proc. Natl. Acad. Sci. U.S.A. 82: 7475–7479.PubMedGoogle Scholar
  2. Andersson, T. Dahlgren, C., Pozzan, T., Stendahl. O. and Lew. D. P., 1986a, Characterization of fMet-Leu-Phe receptor-mediated Cat+ influx across the plasma membrane of human neutrophils. Mol. Pharmacol. 30: 437–443.PubMedGoogle Scholar
  3. Andersson, T., Schlegel, W., Monod, A., Krause. K.-H., Stendahl, O., and Lew, D. P., 1986b, Leukotriene B4 stimulation of phagocytes results in the formation of inositol 1,4,5trisphosphate, Biochem. J. 240: 333–340.PubMedGoogle Scholar
  4. Baggiolini. M., and Dewald, B. 1984, Exocytosis by neutrophils, in: Contemporary Topics in Immunobiology ( R. Snyderman, ed). Vol. 14, pp. 221–246, Plenum Press, New York.Google Scholar
  5. Becker, E. L., Kermode, J. C., Naccache, P. H., Yassin, R., Marsh, M. L., Munoz, J. J., and Sha’afi, R. I., 1985, The inhibition of neutrophil granule enzyme secretion and chemotaxis by pertussis toxin, J. Cell Biol. 100: 1641–1646.PubMedGoogle Scholar
  6. Benovic, J. C., Strasser, R. H., Caron, M. G., and Lefkowitz, R. J., 1986, ß-Adrenergic receptor kinase: Identification of a novel protein kinase that phosphorylates the agonistoccupied form of the receptor, Proc. Natl. Acad. Sci. U.S.A. 83: 2797–2081.PubMedGoogle Scholar
  7. Berridge, M. J., and Irvine, R. F., 1984, Inositol trisphosphate, a novel second messenger in cellular signal transduction, Nature 312: 315–321.PubMedGoogle Scholar
  8. Birnbaumer, L., Codina, J., Mattera, R., Yatani, A., Scherer, N., Toro, M.-J., and Brown, A. M., 1987, Signal transduction by G proteins, in: Molecular Biology and the Kidney (R.Robinson and D. K. Granner, eds.) (in press).Google Scholar
  9. Bokoch, G. M., 1987, The presence of free G protein 3 -y subunits in human neutrophils results in suppression of adenylate cyclase activity, J. Biol. Chem. 262: 589–594.PubMedGoogle Scholar
  10. Bokoch, G. M., and Gilman, A. G., 1984, Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin, Cell 39: 301–308.PubMedGoogle Scholar
  11. Bradford, P. G., and Rubin, R. P., 1985, Characterization of formylmethionyl-leucyl-phenylalanine stimulation of inositol trisphosphate accumulation in rabbit neutrophils, Mol. Pharmacol. 27: 74–78.PubMedGoogle Scholar
  12. Bradford, P. G., and Rubin, R. P., 1986, Quantitative changes in inositol 1,4,5-trisphosphate in chemoattractant-stimulated neutrophils, J. Biol. Chem. 261: 15644–15647.PubMedGoogle Scholar
  13. Brandt, S. J., Dougherty, R. W., Lapetina, E. G., and Niedel, J. E., 1985, Pertussis toxin inhibits chemotactic peptide-stimulated generation of inositol phosphates and lysosomal enzyme secretion in human leukemic (HL-60) cells, Proc. Natl. Acad. Sci. U.S.A. 82: 3277–3280.PubMedGoogle Scholar
  14. Burgess, G. M., McKinney, J. S., Irvine, R. F., and Putney, J. W., Jr., 1985, Inositol 1.4,5trisphosphate and inositol 1,3,4-trisphosphate formation in Ca2+-mobilizing-hormone-activated cells, Biochem. J. 232: 237–243.PubMedGoogle Scholar
  15. Cassel, D., and Selinger, Z., 1977, Mechanism of adenylate cyclase activation by cholera toxin: Inhibition of GTP hydrolysis at the regulatory site, Proc. Natl. Acad. Sci. U.S.A. 74: 3307–3311.PubMedGoogle Scholar
  16. Cockcroft, S., Baldwin, J. M., and Allan, D., 1984, The Cat+-activated polyphosphoinositide phosphodiesterase of human and rabbit neutrophil membranes, Biochem. J. 221: 477–482.PubMedGoogle Scholar
  17. Connolly, T. M., Lawing, W. J., Jr., and Majerus, P. W., 1986, Protein kinase C phosphorylates human platelet inositol trisphosphate 5’-phosphomonoesterase increasing the phosphatase activity, Cell 46: 951–958.PubMedGoogle Scholar
  18. Cox, C. C., Dougherty, R. W., Ganong, B. R., Bell, R. M., Niedel, J. E., and Snyderman, R., 1986, Differential stimulation of the respiratory burst and lysosomal enzyme secretion in human polymorphonuclear leukocytes by synthetic diacylglycerols, J. Immunol. 136: 4611–4616.PubMedGoogle Scholar
  19. Cox, J. A., Jeng, A. Y., Sharkey, N. A., Blumberg, P. M., and Tauber, A. I., 1985, Activation of the human neutrophil nicotinamide adenine dinucleotide phosphate (NADPH)oxidase by protein kinase C, J. Clin. Invest. 76: 1932–1938.PubMedGoogle Scholar
  20. Dewald, B., Payne, T. G., and Baggiolini, M., 1984, Activation of NADPH oxidase of human neutrophils. Potentiation of chemotactic peptide by a diacylglycerol, Biochem. Biophys. Res. Commun. 125: 367–373.PubMedGoogle Scholar
  21. Didsbury, J. R., and Snyderman, R., 1987, Molecular cloning of a novel human GTP-binding protein and its potential role in chemoattractant stimulus—response coupling, Clin. Res., 35: 656A.Google Scholar
  22. Didsbury, J. R., Ho, Y.-S., and Snyderman, R., 1987, Human G, protein a-subunit deduction of amino acid structure from a cloned cDNA, FEBS LETT. 211: 160–164.PubMedGoogle Scholar
  23. Dillon, S. B., Murray, J. J., and Snyderman, R., 1987a, Identification of a novel inositol bisphosphate isomer formed in chemoattractant stimulated human polymorphonuclear leukocytes, Biochem. Biophys. Res. Commun. 144: 264–270.PubMedGoogle Scholar
  24. Dillon, S. B., Murray, J. J., Verghese, M. W., and Snyderman, R., 1987b, Regulation of inositol phosphate metabolism in chemoattractant-stimulated human polymorphonuclear leukocytes: Definition of distinct dephosphorylation pathways for 1P3 isomers, J. Biol. Chem. 262: 11546–11552.PubMedGoogle Scholar
  25. DiVirgilio, F., Vicentini, L. M., Treves, S., Riz, G., and Pozzan, T, 1985, Inositol phosphate formation in fMet-Leu-Phe-stimulated human neutrophils does not require an increase in the cytosolic free Cat± concentration, Biochem. J. 229: 361–367.Google Scholar
  26. Dougherty, R. W., and Niedel, J. E., 1986, Cytosolic calcium regulates phorbol diester binding affinity in intact phagocytes, J. Biol. Chem. 261: 4097–4100.PubMedGoogle Scholar
  27. Dougherty, R. W., Godfrey, P. P., Hoyle, P. C., Putney, J. W., Jr., and Freer, R. J., 1984, Secretagogue-induced phosphoinositide metabolism in human leucocytes, Biochem. J. 222: 307–314.PubMedGoogle Scholar
  28. Falloon, J., Malech, H., Milligan, G., Unson, C., Kahn, R., Goldsmith, P., and Spiegel, A., 1986, Detection of the major toxin substrate of human leukocytes with antisera raised against synthetic peptides, FEBS Lett. 209: 352–356.PubMedGoogle Scholar
  29. Feltner, D. E., Smith, R. H., and Marasco, W. A., 1986, Characterization of the plasma membrane GTPase from rabbit neutrophils: I. Evidence for an Ni-like protein coupled to the formyl peptide, C5a, and leukotriene B4 chemotaxis receptors, J. Immunol. 137: 1961–1970.PubMedGoogle Scholar
  30. Fitzgerald, T. J., Uhing, R. J., and Exton, J. H., 1986, Solubilization of the vasopressin receptor from rat liver plasma membranes: Evidence for a receptor—GTP—binding protein complex, J. Biol. Chem. 261: 16871–16877.PubMedGoogle Scholar
  31. Fletcher, M. P., and Gallin, J. I., 1982, Human neutrophils contain an intracellular pool of putative receptors for the chemoattractant N-formyl methionyllecylphenylalanine with a density of specific granules, J. Cell Biol. 95: 444a.Google Scholar
  32. Fujita, I., Irita, K., Takeshige, K., and Minakami, S., 1984, Diacylglycerol, 1-oleoyl-2acetylglycerol, stimulates superoxide-generation from human neutrophils, Biochem. Biophys. Res. Commun. 120: 318–324.PubMedGoogle Scholar
  33. Gallin, J. I., Sandler, J. A., Clyman, R. I., Manganiello, V. C., and Vaughan, M., 1978, Agents that increases cyclic AMP inhibit accumulation of cGMP and depress human monocyte locomation, J. Immunol. 120: 492–496.PubMedGoogle Scholar
  34. Gardner, J. P., Melnick, D. A., and Malech, H. L., 1986, Characterization of the formyl peptide chemotactic receptor appearing at the phagocytic cell surface after exposure to phorbol myristate acetate, J. Immunol. 136: 1400–1405.PubMedGoogle Scholar
  35. Gennaro, R., Florio, C., and Romeo, D., 1986, Coactivation of protein kinase C and NADPH oxidase in the plasma membrane of neutrophil cytoplasts, Biochem. Biophys. Res. Commun. 134: 305–312.PubMedGoogle Scholar
  36. Giershik, P. Falloon, J., Milligan, G. Pines, M., Gallin, J. I. and Spiegel, A., 1986. Immunochemical evidence for a novel pertussis toxin substrate in human neutrophils, J. Biol. Chem. 261: 8058–8062.Google Scholar
  37. Gilman, A. G., 1984, G proteins and dual control of adenylate cyclase, Cell 36: 577–579.PubMedGoogle Scholar
  38. Goetzl, E. J., Foster, D. W., and Goldman, D. W.. 1981, Isolation and partial characterization of membrane protein constituents of human neutrophil receptors for chemotactic for-mylmethionyl peptides, Biochemistry 20: 5717–5722.PubMedGoogle Scholar
  39. Goldman. D. W. Chang, F. H., Gifford. L. A., Goetzl, E. J.. and Bourne, H. R., 1985, Pertussis toxin inhibition of chemotactic factor-induced calcium mobilization and function in human polymorphonuclear leukocytes, J. Exp. Med. 162: 145–156.PubMedGoogle Scholar
  40. Goldstein, I. M., 1984. Neutrophil degranulation, in: Contemporary Topics in Immunobiolog ( R. Snyderman, ed.), Vol. 14, pp. 189–220, Plenum Press, New York.Google Scholar
  41. Ho, Y.-S., Lee, W. M. F., and Snyderman, R., 1987, Chemoattractant-induced activation of c-fos gene expression, J. Exp. Med. 165: 1524–1539.PubMedGoogle Scholar
  42. Honeycutt, P. J., and Niedel, J. E., 1986, Cytochalasin B enhancement of the diacylglycerol response in formyl-stimulated neutrophils, J. Biol. Chem. 261: 15900–15905.PubMedGoogle Scholar
  43. Hoyle, P. C., and Freer, R. J., 1984, Isolation and reconstitution of the N-formylpeptide receptor from HL-60 derived neutrophils, FEBS Lett. 167: 277–280.PubMedGoogle Scholar
  44. Huang, C.-K., 1987, Partial purification and characterization of formylpeptide receptor from rabbit peritoneal neutrophils, J. Leukocyte Biol. 41: 63–69.PubMedGoogle Scholar
  45. Jesaitis, A. J., Naemura, J. R., Painter, R. G., Sklar, L. A., and Cochrane, C. G., 1982, Intracellular localization of N-formyl chemotactic receptor and Mgt+ dependent ATPase in human granulocytes, Biochim. Biophys. Acta. 719: 556–568.PubMedGoogle Scholar
  46. Kay, G. E., Lane, B. C., and Snyderman, R., 1983, Induction of selective biological responses to chemoattractants in a human monocyte-like cell line, Infect. Immun. 41: 1166–1174.PubMedGoogle Scholar
  47. Kikuchi, A., Kozawa, O., Kaibuchi, K., Katada, T., Ui, M., and Takai, Y., 1986, Direct evidence for involvement of a guanine nucleotide-binding protein in chemotactic peptide-stimulated formation of inositol bisphosphate and trisphosphate in differentiated leukemic (HL-60) cells: Reconstitution with Gi or Go of the plasma membranes ADP-ribosylated by pertussis toxin, J. Biol. Chem. 257: 11558–11562.Google Scholar
  48. Koo, C., Lefkowitz, R. J., and Snyderman, R., 1982, The oligopeptide chemotactic factor receptor on human polymorphonuclear leukocyte membranes exists in two affinity states, Biochem. Biophys. Res. Commun. 106: 442–449.PubMedGoogle Scholar
  49. Koo, C., Lefkowitz, R. J., and Snyderman, R., 1983, Guanine nucleotides modulate the binding affinity of the oligopeptide chemoattractant receptor on human polymorphonuclear leukocytes, J. Clin. Invest. 72: 748–753.PubMedGoogle Scholar
  50. Korchak, H. M., Rutherford, L. E., and Weissmann, G., 1984a, Stimulus response coupling in the human neutrophil: I. Kinetic analysis of changes in calcium permeability, J. Biol. Chem. 259: 4070–4075.PubMedGoogle Scholar
  51. Korchak, H. M., Vienne, K.. Rutherford, L. E., Wilkenfeld, C., Finkelstein, M. C., and Weissmann, G., 1984b, Stimulus response coupling in the human neutrophil: II. Temporal analysis of changes in cytosolic calcium and calcium efflux, J. Biol. Chem. 259: 4076–4082.PubMedGoogle Scholar
  52. Lad, P. M., Olson, C. V., Grewal, I. S., and Scott, S. J., 1985a, A pertussis toxin-sensitive GTP-binding protein in the human neutrophil regulates multiple receptors, calcium mobilization, and lectin-induced capping, Proc. Natl. Acad. Sci. U.S.A. 82: 8643–8647.PubMedGoogle Scholar
  53. Lad, P. M., Olson, C. V., and Smiley, P. A., 1985b, Association of the N-formyl-Met-LeuPhe receptor in human neutrophils with a GTP-binding protein sensitive to pertussis toxin, Proc. Natl. Acad. Sci. U.S.A. 82: 869–873.PubMedGoogle Scholar
  54. Lehmeyer, J. E., Snyderman, R., and Johnston, R. B., Jr., 1979, Stimulation of neutrophil oxidative metabolism by chemotactic peptides: Influence of calcium ion concentration and cytochalasin B and comparison with stimulation by phorbol myristate acetate, Blood 54: 35–45.PubMedGoogle Scholar
  55. Lew, P. D., Wollheim, C. B., Waldvogel, F. A., and Pozzan, T., 1984, Modulation of cytosolic-free calcium transients by changes in intracellular calcium-buffering capacity: Correlation with exocytosis and 02- production in human neutrophils, J. Cell Biol. 99: 1212–1220.PubMedGoogle Scholar
  56. Lew, P. D., Monod, A., Krause, K.-H., Waldvogel, F. A., Biden, T. J., and Schlegel, W., 1986a, The role of cytosolic calcium in the generation of inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate in HL-60 cells: Differential effects of chemotactic peptide receptor stimulation at distinct Cat+ levels, J. Biol. Chem. 261: 13121–13127.PubMedGoogle Scholar
  57. Lew, P. D., Monod, A., Waldvogel, F. A., Dewald, B., Baggiolini, M., and Pozzan, T., 1986b, Quantitative analysis of the cytosolic free calcium dependency of exocytosis from three subcellular compartments in intact neutrophils, J. Cell Biol. 102: 2197–2204.PubMedGoogle Scholar
  58. Mackin, W. M., Huang, C. K., and Becker, E. L., 1982, The formyl peptide chemotactic receptor on rabbit peritoneal neutrophils, J. Immunol. 129: 1608–1611.PubMedGoogle Scholar
  59. Majerus, P. W., Connolly, T. M., Deckmyn, H., Ross, T. S., Bross, T. E., Ishii, H., Bansal, V. S., and Wilson, D. B., 1986, The metabolism of phosphoinositide-derived messenger molecules, Science 234: 1519–1526.PubMedGoogle Scholar
  60. Malech, H. L., Gardner, J. P., Heiman, D. F., and Rosenzweig, S. A., 1985, Asparagine-linked oligosaccharides on formyl peptide chemotactic receptors of human phagocytic cells, J. Biol. Chem. 260: 2509–2514.PubMedGoogle Scholar
  61. McPhail, L. C., and Snyderman, R., 1984, Mechanisms of regulating the respiratory burst in leukocytes, in: Contemporary Topics in Immunobiology: Regulation of Leukocyte Function ( R. Snyderman, ed.), pp. 247–281, Plenum Press, New York.Google Scholar
  62. McPhail, L. C., Wolfson, M., Clayton, C., and Snyderman, R., 1984, Protein kinase C and neutrophil (PMN) activation: Differential effects of chemoattractants and phorbol myristate acetate (PMA), Fed. Proc. 43: 1661 (Abstract).Google Scholar
  63. Melloni, E., Pontremoli, S., Salamino, F., Sparatore, B., Michetti, M., Sacco, O., and Horeker, B. L., 1986, ATP induces the release of a neutral serine proteinase and enhances the production of superoxide anion in membranes from phorbol ester-activated neutrophils, J. Biol. Chem. 261: 11437–11439.PubMedGoogle Scholar
  64. Mitchell, R. L., Zokas, L., Schreiber, R. D., and Yema, I. M., 1985, Rapid induction of the expression of proto-oncogene fos during human monocytic differentiation, Cell 40: 209–217.PubMedGoogle Scholar
  65. Molina, Y., Vedia, L., and Lapetina, E. G., 1986, Phorbol 12,13-dibutyrate and 1-oleyl-2acetyldiacylglycerol stimulate inositol trisphosphate dephosphorylation in human platelets, J. Biol. Chem. 261: 10493–10495.Google Scholar
  66. Molski, T. F. P., Naccache, P. H., Marsah, M. L., Kermode, J., Becker, E. L., and Sha’afi, R. I., 1984, Pertussis toxin inhibits the rise in the intracellular concentration of free calcium that is induced by chemotactic factors in rabbit neutrophils: Possible role of the “G proteins” in calcium mobilization, Biochem. Biophys. Res. Commun. 124: 644–650.PubMedGoogle Scholar
  67. Muller, R., Muller, D., and Guilbert, L., 1984, Differential expression of c-fos in hematopoietic cells: Correlation with differentiation of monomyelocytic in vitro, EMBO J. 3: 1887–1890.PubMedGoogle Scholar
  68. Myers, M. A., McPhail, L. C., and Snyderman, R., 1985, Redistribution of protein kinase C activity in human monocytes: Correlation with activation of the respiratory burst, J. Immunol. 135: 3411–3416.PubMedGoogle Scholar
  69. Naccache, P. H., Molski. T. F. P. Borgeat, P., White, J. R.. and Sha’afi, R. I., 1985, Phorbol esters inhibit the fMet-Leu-Phe-and leukotriene B.;-stimulated calcium mobilization and enzyme secretion in rabbit neutrophils, J. Biol. Chem. 260: 2125–2131.PubMedGoogle Scholar
  70. Neer, E. J., Lok. J. M., and Wolf, L. G.. 1984, Purification and properties of the inhibitory guanine nucleotide regulatory unit of brain adenylate cyclase, J. Biol. Chem. 259: 14222–14229.PubMedGoogle Scholar
  71. Niedel, J., Kahane. I.. and Cuatrecases, P., 1979, Receptor-mediated internalization of fluorescent chemotactic peptide by human neutrophils, Science 205: 1412–1414.PubMedGoogle Scholar
  72. Niedel, J., David. J., and Cuatrecasas, P., 1980, Covalent affinity labeling of the formyl peptide chemotactic receptor, J. Biol. Chem. 255:7063–7066.PubMedGoogle Scholar
  73. Nishihira, J., McPhail, L. C., and O’Flaherty, J. T., 1986, Stimulus-dependent mobilization of protein kinase C, Biochem. Biophys. Res. Commun. 134: 587–594.PubMedGoogle Scholar
  74. O’Flaherty, J. T., Schmitt, J. D., McCall, C. E., and Wykle, R. L., 1984, Diacylglycerols enhance human neutrophil degranulation responses: Relevancy to a multiple mediator hypothesis of cell function, Biochem. Biophys. Res. Commun. 123: 64–70.PubMedGoogle Scholar
  75. Ohta, H., Okajima, F., and Ui, M., 1985, Inhibition by islet-activating protein of a chemotactic peptide-induced early breakdown of inositol phospholipids and Cas2+ mobilization in guinea pig neutrophils, J. Biol. Chem. 260: 15771–15780.PubMedGoogle Scholar
  76. Okajima, F., and Ui, M., 1984, ADP-ribosylation of the specific membrane protein by islet-activating protein, pertussis toxin, associated with inhibition of a chemotactic peptide-induced arachidonate release in neutrophils, J. Biol. Chem. 259: 13863–13871.PubMedGoogle Scholar
  77. Okajima, F., Katada, T., and Ui, M., 1985, Coupling of the guanine nucleotide regulatory protein to chemotactic peptide receptors in neutrophil membranes and its uncoupling by islet-activating protein, pertussis toxin. A possible role of the toxin substrate in Cat+_ mobilizing receptor-mediated signal transduction, J. Biol. Chem. 260: 6761–6768.PubMedGoogle Scholar
  78. Painter, R. G., Schmitt, M., Jesaitis, A. J., Sklar, L. A., Aissnar, K., and Cochrane, C. G., 1982, Photoaffinity labeling of the N-formyl peptide receptor on human polymorphonuclear leukocytes, J. Cell. Biochem. 20: 203–214.PubMedGoogle Scholar
  79. Palmblad, J., Gyllenhammar, H., Lindgren, J. A., and Malmsten, C. L., 1984, Effects of leukotrienes and f-Met-Leu-Phe on oxidative metabolism of neutrophils and eosinophils, J. Immunol. 132: 3041–3045.PubMedGoogle Scholar
  80. Pike, M. C., Jakoi, L., McPhail, L.C., and Snyderman, R., 1986, Chemoattractant-mediated stimulation of the respiratory burst in human polymorphonuclear leukocytes may require appearance of protein kinase C in the cells’ particulate fraction, Blood 67: 909–913.PubMedGoogle Scholar
  81. Polakis, P., and Snyderman, R., 1987, G-protein-chemoattractant receptor interaction: Co-purification of the formylpeptide receptor with a guanine nucleotide binding protein, Clin. Res. 35: 487A.Google Scholar
  82. Pozzan, T., Lew, D. P., Wollheim, C. B., and Tsien, R. Y., 1983, Is cytosolic ionized calcium regulating neutrophil activation?, Science 221: 1413–1415.PubMedGoogle Scholar
  83. Preiss, J., Loomis, C. R., Bishop, W. R., Stein, R., Niedel, J. E., and Bell, R. M., 1986, Quantitative measurement of sn-1,2-diacylglycerols present in platelets, hepatocytes and ras- and sis-transformed normal rat kidney cells, J. Biol. Chem. 261:8597–8600.Google Scholar
  84. Prentki, M., Wollheim, C. G., and Lew, P. D., 1984, Cat+ homeostatis in permeabilized human neutrophils: Characterization of Cat+-sequestering pools and the action of inositol 1,4,5-trisphosphate, J. Biol. Chem. 259: 13777–13782.PubMedGoogle Scholar
  85. Rivkin, I., Rosenblatt, J., and Becker, E. L., 1975, The role of cyclic AMP in the chemotactic responsiveness and spontaneous motility of rabbit peritoneal neutrophils, J. Immunol. 115: 1126–1134.PubMedGoogle Scholar
  86. Serhan, C. N., Radin, A., Smolen, J. E., Korchak, H., Samuelsson, B., and Weissman, G., 1982, Leukotriene, B4 is a complete secretogogue in human neutrophils: A kinetic analysis, Biochem. Biophys. Res. Commun. 107: 1006–1012.PubMedGoogle Scholar
  87. Serhan, C. N., Broekman, M. J., Korchak, H. M., Smolen, J. E., Marcus, A. J., and Weissman, G., 1983, Changes in phosphatidylinositol and phosphatidic acid in stimulated human neutrophils: Relationship to calcium mobilization, aggregation and superoxide radical generation, Biochim. Biophys. Acta 762: 420–428.PubMedGoogle Scholar
  88. Shichi, H., and Somers, R. L., 1978, Light-dependent phosphorylation of rhodopsin: Purification and properties of rhodopsin kinase, J. Biol. Chem. 253: 7040–7046.PubMedGoogle Scholar
  89. Showell, H. J., Freer, R. J., Zigmond, S. H., Schiffmann, E., Aswanikumar, S., Corcoran, B., and Becker, E. L., 1976, The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal enzyme secretion for neutrophils, J. Exp. Med. 143: 1154–1169.PubMedGoogle Scholar
  90. Simchowitz, L., Fischbein, L. C., Spilberg, I., and Atkinson, J. P., 1980, Induction of a transient elevation in intracellular levels of adenosine-3’, 5’-cyclic monophosphate by chemotactic factors: An early event in human neutrophil activation, J. Immunol. 124: 1482–1491.PubMedGoogle Scholar
  91. Sklar, L. A., Jesaitis, A. J., and Painter, R. G., 1984, The neutrophil N-formyl peptide receptor: Dynamics of ligand—receptor interactions and their relationship to cellular responses, Contemp. Topics Immunobiol. 14: 29–82.Google Scholar
  92. Sklar, L. A., Bokoch, G. M., Button, D., and Smolen, J. E., 1987, Regulation of ligand—receptor dynamics by guanine nucleotides: Real-time analysis of interconverting states for the neutrophil formylpeptide receptor, J. Biol. Chem. 262: 135–139.PubMedGoogle Scholar
  93. Smith, C. D., Lane, B. C., Kusaka, I., Verghese, M. W., and Snyderman, R., 1985, Chemoattractant-receptor induced hydrolysis of phosphatidylinositol 4,5-bisphosphate in human polymorphonuclear leukoctye membranes: Requirement of a guanine nucleotide regulatory protein, J. Biol. Chem. 260: 5875–5878.PubMedGoogle Scholar
  94. Smith, C. D., Cox, C. C., and Snyderman, R., 1986, Receptor-coupled activation of phosphoinositide-specific phospholipase C by an N protein, Science 232: 97–100.Google Scholar
  95. Smith, C. D., Uhing, R. J., and Snyderman, R., 1987, Nucleotide regulatory protein-mediated activation of phospholipase C in human polymorphonuclear leukocytes is disrupted by phorbol esters, J. Biol. Chem. (in press).Google Scholar
  96. Snyderman, R., and Pike, M. C., 1984a, Regulation of leukocyte function, in: Contemporary Topics in Immunobiology ( R. Snyderman, ed.), pp. 1–28, Plenum Press, New York.Google Scholar
  97. Snyderman, R., and Pike, M. C., 1984b, Chemoattractant receptors on phagocytic cells, in: Annual Review of Immunology, ( W. E. Paul, ed.), Vol. 2, pp. 257–281. Annual Reviews, Inc., Palo Alto, CA.Google Scholar
  98. Snyderman, R., and Uhing, R. J., 1987, Stimulus—response coupling mechanisms, in: Inflammation: Basic Principles and Clinical Correlates (J. I. Gallin, I. M. Goldstein, and R. Snyderman, eds.), pp. 309–323, Raven Press, New York.Google Scholar
  99. Snyderman, R., Pike, M. C., Edge, S., and Lane, B., 1984, A chemoattractant receptor on macrophages exists in two affinity states regulated by guanine nucleotides, J. Cell Biol. 98: 444–448.PubMedGoogle Scholar
  100. Snyderman, R., Smith, C. D., and Verghese, M. W., 1986, Model for leukocyte regulation by chemoattractant receptors: Roles of a guanine nucleotide regulatory protein and polyphosphoinositide metabolism, J. Leukocyte Biol. 40: 785–800.PubMedGoogle Scholar
  101. Spiegel, A. M., 1987, Signal transduction by guanine nucleotide binding proteins, Mol. Cell. Endocrinol. 49: 1–16.PubMedGoogle Scholar
  102. Sullivan, S., and Zigmond, S., 1980, Chemotactic peptide receptor modulation in polymorphonuclear leukocytes, J. Cell Biol. 85: 703–711.PubMedGoogle Scholar
  103. Takenawa, T., lshitoya, J., and Nagai, Y., 1986, Inhibitory effect of prostaglandin E2, forskolin, and dibutyryl cAMP on arachidonic acid release and inositol phospholipid metabolism in guinea pig neutrophils, J. Biol. Chem. 261: 1092–1098.PubMedGoogle Scholar
  104. Truett, A. P., III, Verghese, M. W., Dillon, S. B., and Snyderman, R., 1987, Leukocyte (PMN) activation by chemoattractants (CTX): A two phase sequential pathway mediates the respiratory burst, Clin. Res. 35: 618A.Google Scholar
  105. Verghese, M. W., Fox, K., McPhail, L. C., and Snyderman, R., I985a, Chemoattractantelicited alterations of cAMP levels in human polymorphonuclear leukocytes require a Ca -dependent mechanism which is independent of transmembrane activation of adenylate cyclase, J. Biol. Chem. 260: 6769–6775.PubMedGoogle Scholar
  106. Verghese, M. W., Smith, C. D., and Snyderman, R., I985b, Potential role for a guanine nucleotide regulatory protein in chemoattractant receptor mediated polyphosphoinositide metabolism, Ca+ + mobilization and cellular responses by leukocytes, Biochem. Biophys. Res. Commun. 127: 450–457.Google Scholar
  107. Verghese, M. W., Smith, C. D., and Snyderman, R., 1985e, Role for a guanine nucleotide regulatory (N) protein in chemoattractant mediated Cat+ mobilization and cAMP formation in human neutrophils (PMNs), Clin. Res. 33: 566A.Google Scholar
  108. Verghese, M. W., Smith, C. D., Charles, L. A., Jakoi, L., and Snyderman, R., 1986a, A guanine nucleotide regulatory protein controls polyphosphoinositide metabolism, Cat+ mobilization and cellular responses to chemoattractants in human monocytes, J. Immunol. 137: 271–275.PubMedGoogle Scholar
  109. Verghese, M. W., Smith, C. D., Charles, L. A., and Snyderman, R., 1986b, A common transduction pathway for leukocyte chemoattractant receptors: Phospholipase C activation by a guanine nucleotide regulatory protein, Clin. Res. 34: 679A.Google Scholar
  110. Verghese, M. W., Uhing, R. J., and Snyderman, R., 1986e, A pertussis/cholera toxin-sensitive N protein may mediate chemoattractant receptor signal transduction, Biochem. Biophys. Res. Commun. 138: 887–894.PubMedGoogle Scholar
  111. Volpi, M., Nacchache, P. H., Molski, T. F. P., Shefcyk, J., Huang, C. K., Marsh, M. L., Munoz, J., Becker, E. L., and Sha’afi, R. I., 1985, Pertussis toxin inhibits fMet-Leu-Phebut not phorbol ester-stimulated changes in rabbit neutrophils: Role of G proteins in excitation response coupling, Proc. Natl. Acad. Sci. U.S.A. 82: 2708–2712.PubMedGoogle Scholar
  112. White, J. R., Huang, C.-K., Hill, J. M., Jr., Naccache, P. H., Becker, E. L., and Sha’afi, R. I., 1984, Effect of phorbol 12-myristate 13-acetate and its analogue 4a-phorbol 12,13didecanoate on protein phosphorylation and lysosomal enzyme release in rabbit neutrophils, J. Biol. Chem. 259: 8605–8611.PubMedGoogle Scholar
  113. Williams, L. T., Snyderman, R., Pike, M. C., and Lefkowitz, R. J., 1977, Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes, Proc. Natl. Acad. Sci. U.S.A. 74: 1204–1208.PubMedGoogle Scholar
  114. Wolfson, M., McPhail, L. C., Nasrallah, V. N., and Snyderman, R., 1985, Phorbol myristate acetate mediates redistribution of protein kinase C in human neutrophils: Potential role in the activation of the respiratory burst enzyme, J. Immunol. 135: 2057–2062.PubMedGoogle Scholar
  115. Yuli, I., and Snyderman, R., 1986, Extensive hydrolysis of N-formyl-L-methionyl-L-leucyl-L-[3H]phenylalanine by human polymorphonuclear leukocytes: A potential mechanism for modulation of the chemoattractant signal, J. Biol. Chem. 261: 4902–4908.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Ronald J. Uhing
    • 1
  • Susan B. Dillon
    • 1
  • Paul G. Polakis
    • 1
  • Artis P. TruettIII
    • 1
  • Ralph Snyderman
    • 1
  1. 1.Howard Hughes Medical Institute and the Division of Rheumatology and Immunology, Department of MedicineDuke University Medical CenterDurhamUSA

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