Skip to main content
SpringerLink
Log in

Chemotactic peptides

Mechanisms, functions, and possible role in inflammatory bowel disease

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

An important component of host defenses is the ability of inflammatory cells to detect and respond to minute concentrations of chemoattractant substances. Chemotactic peptides elaborated by both bacteria and leukocytes are the focus of this review. These peptides induce directed migration of inflammatory cells towards their targets, and stimulate biological functions including degranulation, release of oxygen radicals, phagocytosis, and eicosanoid production. Among the released eicosanoids, leukotriene B4 potentiates the leukocyte response. As with other chemotactic factors, these functions are regulated partially through differential coupling to high- and low-affinity receptors and via calcium as the second messenger. Some chemotactic peptides are elaborated by normal colonic luminal bacteria. Recent evidence demonstrates that these peptides can produce mucosal inflammation in vivo. A possible mechanism for this effect involves abnormal colonic permeability in susceptible individuals that allows bacterial chemotactic peptides access to the mucosa where they may induce inflammation. Remaining questions include the mechanism by which the mucosal barrier is breached and the role of leukotrienes in the potentiation of colonic inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Williams LT, Snyderman R, Pike MC, Lefkowitz RJ: Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes. Proc Natl Acad Sci USA 74:1204–1208, 1977

    PubMed  Google Scholar 

  2. Ward PA, Cochrane CG, Muller-Eberhard HJ: Further studies on the chemotactic factor of complement and its formation in vivo. Immunology 11:141–153, 1966

    PubMed  Google Scholar 

  3. Snyderman R, Phillips J, Mergenhagen SE: Polymorphonuclear leukocyte chemotactic activity in rabbit serum and guinea pig serum treated with immune complexes: Evidence for C5a as the major chemotactic factor. Infect Immunity 1:521–525, 1970

    Google Scholar 

  4. Goetzl EJ: Regulation of the polymorphonuclear leukocyte chemotactic response by immunological reactions.In Leukocyte Chemotaxis: Methods, Physiology, and Clinical Implications. JI Gallin, PG Quie (eds). New York, Raven Press, 1978, pp 161–178

    Google Scholar 

  5. Chenoweth DE: Complement mediators of inflammation.In Immunobiology of the Complement System. GD Ross (ed). New York, Academic Press, 1986, pp 63–86

    Google Scholar 

  6. Movat HZ, Rettl C, Burrows CE, Johnston MG: Thein vivo effect of leukotriene B4 on polymorphonuclear leukocytes and the microcirculation. Am J Pathol 115:233–244, 1984

    PubMed  Google Scholar 

  7. Turner SR, Campbell JA, Lynn WS: Polymorphonuclear leukocyte chemotaxis toward oxidized lipid components of cell membranes. J Exp Med 141:1437–1441, 1975

    PubMed  Google Scholar 

  8. Day NK, Good RA: Biological Amplification Systems in Inflammation. Plenum Medical Book Co., New York, 1977, pp 162–168

    Google Scholar 

  9. Schiffmann E, Showell HV, Corcoran BA, Ward PA, Smith E, Becker EL: The isolation and partial characterization of neutrophil chemotactic factors fromEscherichia coli. J Immunology 114:1831–1837, 1975

    Google Scholar 

  10. Shiffmann E, Corcoran BA, Wahl SM:N-Formylmethionyl peptides as chemoattractants for leukocytes. Proc Natl Acad Sci USA 72:1059–1062, 1975

    PubMed  Google Scholar 

  11. Showell HJ, Freer RJ, Zigmon SH, Schiffman E, Aswanikumar S, Corcoran B, Becker EL: The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal enzyme secretion for neutrophils. J Exp Med 143:1154–1169, 1976

    PubMed  Google Scholar 

  12. Ho PPK, Young AL, Southard GL: Methyl ester ofN-formylmethionyl-leucyl-phenylalanine. Arthritis Rheum 21:133–136, 1978

    PubMed  Google Scholar 

  13. Temple TR, Snyderman R, Jordan HV, Mergenhagen SE: Factors from saliva and oral bacteria chemotactic for polymorphonuclear leukocytes: Their possible role in gingival inflammation. J Periodontol 41:71–80, 1970

    PubMed  Google Scholar 

  14. Marasco WA, Phan SH, Krutzsch H, Showell HJ, Feltner DE, Nairn R, Becker EL, Ward PA; Purification and identification of formyl-methionyl-leucyl-phenylalanine as the major peptide neutrophil chemotactic factor produced byEscherichia coli. J Biol Chem 259:5430–5439, 1984

    PubMed  Google Scholar 

  15. Miyake Y, Yashuhara T, Fukui K, Suginaka H, Nakajima T, Moriyama T: Purification and characterization of neutrophil chemotactic factors ofStreptococcus sanguis. Biochim Biophys Acta 758:181–186, 1983

    PubMed  Google Scholar 

  16. Wasserman SI, Goetzl EJ, Austen KF: Preformed eosinophil chemotactic factor of anaphylaxis. J Immunol 112:351–358, 1974

    PubMed  Google Scholar 

  17. Keller HU, Storin E: Studies on chemotaxis. V. On the chemotactic effect of bacteria. Int Arch Allergy 31:505–517, 1967

    Google Scholar 

  18. Ward PA, Leprow IH, Newman LJ: Bacterial factors chemotactic for polymorphonuclear leukocytes. Am J Pathol 52:725–736, 1968

    PubMed  Google Scholar 

  19. Aswanikumar S, Schiffman E, Corcoran BA, Pert CB, Morell JL, Gross E: Antibiotics and peptides with agonist and antagonist chemotactic activity. Biochem Biophys Res Commun 80:464–471, 1978

    PubMed  Google Scholar 

  20. Freer RJ, Day AR, Becker EL, Showell HJ, Schiffmann E, Gross E: Structural requirements for synthetic peptide chemoattractants and antagonists. Proceedings, Sixth American Peptide Symposium, Georgetown University, E Gross, J Meienhofer (eds). Rockford, Illinois, Pierce Chemical 1979, pp 749–751

    Google Scholar 

  21. Schiffmann E, Venkatasubramanian K, Corcoran B, Aswanikaumar S, Day AR, Freer RJ, Gallin JI, Hirata F, Clark RA, Brown JH, Gross E: Chemotactic peptides as probes of molecular events in leukocyte chemotaxis. Proceedings, Sixth American Peptide Symposium, Georgetown University, E Gross, J Meienhofer (eds). Rockford, Illinois, Pierce Chemical 1979, pp 731–741

    Google Scholar 

  22. Clark RA, Szot R, Venkatasobramanian K, Schiffmann E: Chemotactic factor inactivation by myeloperoxidase-mediated oxidation of methionine. J Immunol 124:2020–2026, 1980

    PubMed  Google Scholar 

  23. Adams JM, Capecchi MR:N-Formylmethionyl-ionyl-sRNA as the initiator of protein synthesis. Proc Natl Acad Sci USA 55:147–155, 1966

    PubMed  Google Scholar 

  24. Freer RJ, Day AR, Radding JA, Schiffmann E, Aswanikumar S, Showell HJ, Becker EL: Further studies on the structural requirements for synthetic peptide chemoattractants. Biochemistry 19:2404–2410, 1980

    PubMed  Google Scholar 

  25. Kay AB, Stechschulte DJ, Austen KF: An eosinophil leukocyte chemotactic factor of anaphylaxis. J Exp Med 133:602–619, 1971

    PubMed  Google Scholar 

  26. Kay AB, Austen KF: IgE-mediated release of an eosinophil leukocyte chemotactic factor from human lung. J Immunol 107:899–902, 1971

    PubMed  Google Scholar 

  27. Wasserman SI, Goetzl EJ, Austen KF: Inactivation of slow-reacting substance of anaphylaxis by human eosinophil arylsulfatase. Immunology 114:645–649, 1975

    Google Scholar 

  28. Wasserman SI, Whitmer D, Goetzl EJ, Austen KF: Chemotactic deactivation of human eosinophils by the eosinophilic chemotactic factor of anaphylaxis. Proc Soc Exp Biol Med 148:301–306, 1975

    PubMed  Google Scholar 

  29. Turnbull LW, Evans DP, Kay AB: Human eosinophils, acidic tetrapeptides (ECF-A) and histamine. Immunology 32:57–63, 1977

    PubMed  Google Scholar 

  30. Goetzl EJ, Austen KF: Structural determinants of the eosinophil chemotactic activity of the acidic tetrapeptides of eosinophil chemotactic factor of anaphylaxis. J Exp Med 144:1424–1437, 1976

    PubMed  Google Scholar 

  31. Goetzl EJ, Austen F: Purification and synthesis of eosinophilic tetrapeptides of human lung tissue: Identification as eosinophil chemotactic factor of anaphylaxis. Proc Natl Acad Sci USA 72:4123–4127, 1975

    PubMed  Google Scholar 

  32. Aswanikumar S, Corcoran B, Schiffmann E: Demonstration of a receptor on rabbit neutrophils for chemotactic peptides. Biochem Biophys Res Commun 74:810–817, 1977

    PubMed  Google Scholar 

  33. Pike MC, Fischer DG, Koren HS, Snyderman R: Development of specific receptors forN-formylated chemotactic peptides in a human monocyte cell line stimulated with lymphokines. J Exp Med 152:31–410, 1980

    PubMed  Google Scholar 

  34. O'Flaherty JT, Showell HJ, Kreutzer DL, Ward PA, Becker EL: Inhibition ofin vivo andin vitro neutrophil responses to chemotactic factors by a competitive antagonist. J Immunol 120:1326–1332, 1978

    PubMed  Google Scholar 

  35. Atkinson JP, Sinchowitz L, Mehta J, Stenson WF: 5,8,11,14-Eicosatetraynoic acid (ETYA) inhibits binding ofN-formyl-methionyl-leucyl-phenylalanine (FMLP) to its receptor on human granulocytes. Immunopharmacol 4:1–9, 1982

    Google Scholar 

  36. Perez HD, Ong RR, Elfman F: Removal or oxidation of surface membrane sialic acid inhibits formyl-peptide-induced polymorphonuclear leukocyte chemotaxis. J Immunol 134:1902–1908, 1985

    PubMed  Google Scholar 

  37. Snyderman R, Pike MC: Pathophysiologic aspects of leukocyte chemotaxis: Identification of a specific chemotactic factor binding site on human granulocytes and defects of macrophage function associated with neoplasia.In Leukocyte Chemotaxis: Methods, Physiology, and Clinical Implications, JI Gallin, PG Quie (eds). New York, Raven Press, 1978, pp 357–378

    Google Scholar 

  38. Painter RG, Sklar LA, Jesaitis AJ, Schmitt M, Cochrane CG: Activation of neutrophils byN-formyl chemotactic peptides. Fed Proc 43:2737–2742, 1984

    PubMed  Google Scholar 

  39. Smith RJ, Iden SS, Bowman BJ: Activation of the human neutrophil secretory process with 5(s), 12 (R)-dihydroxy-6,14-cis-8,10-trans-eicosatetranoic acid. Inflammation 8:365–384, 1984

    PubMed  Google Scholar 

  40. Koo C, Lefkowitz RJ, Snyderman R: The oligopeptide chemotactic factor receptor on human polymorphonuclear leukocyte membranes exists in two affinity states. Biochem Biophys Res Commun 106:442–449, 1982

    PubMed  Google Scholar 

  41. Yuli I, Tomonaga A, Snyderman R: Chemoattractant receptor functions in human polymorphonuclear leukocytes are divergently altered by membrane fluidizers. Proc Natl Acad Sci USA 79:5906–5910, 1982

    PubMed  Google Scholar 

  42. Snyderman R: Regulatory mechanisms of a chemoattractant receptor on leukocytes. Fed Proc 43:2743–2748, 1984

    PubMed  Google Scholar 

  43. Lohr KM, Snyderman R: Amphotericin B alters the affinity and functional activity of the oligopeptide chemotactic factor receptor on human polymorphonuclear leukocytes. J Immunol 129:1594–1599, 1982

    PubMed  Google Scholar 

  44. Gallin JI, Seligmann B, Fletcher M: Dynamics of human neutrophil receptors for the chemoattractant f-Met-Leu-Phe. Agents Actions Suppl 12:290–308, 1983

    PubMed  Google Scholar 

  45. Niedel J, Wilkinson S, Cuatrecasas P: Receptor-mediated uptake and degradation of125I-chemotactic peptide by human neutrophils. J Biol Chem 254:10,700–10,706, 1979

    Google Scholar 

  46. Gallin JI, Seligmann BE: Mobilization and adaptation of human neutrophil chemoattractant f-Met-Leu-Phe receptors. Fed Proc 43:2732–2736, 1984

    PubMed  Google Scholar 

  47. Sinchowitz L, Spilberg I, Atkinson JP: Evidence that functional responses of human neutrophils occur independently of transient elevations in cyclic AMP levels. J Cyclic Nucleotide Protein Phosphoryl Res 9:35–47, 1983

    Google Scholar 

  48. Korchak HM, Vienne K, Rutherford LE, Weissmann G: Neutrophil stimulation: receptor, membrane, and metabolic events. Fed Proc 43:2749–2754, 1984

    PubMed  Google Scholar 

  49. Bormann BJ, Huang CK, Macin WM, Becker EL: Receptor-mediated activation of a phospholipase A2 in rabbit neutrophil plasma membrane. Proc Natl Acad Sci USA 81:767–770, 1984

    PubMed  Google Scholar 

  50. Takenawa T, Homma Y, Nagai Y: Role of Ca2+ in phosphatidylinositol response and arachidonic acid release in formylated tripeptide or Ca2+ ionophore A23187-stimulated guinea pig neutrophils. J Immunol 130:2849–2855, 1983

    PubMed  Google Scholar 

  51. White JR, Naccache PH, Molski TFP, Borgeat P, Sha'afi RI: Direct demonstration of increased intracellular concentration of free calcium in rabbit and human neutrophils following stimulation by chemotactic factor. Biochem Biophys Res Commun 113:44–50, 1983

    PubMed  Google Scholar 

  52. Becker EL, Naccache PH, Showell HM, Sha'afi Ri: Synthetic chemotactic peptides as initiators of multiple biologic functions of the neutrophil: The role of calcium. Proceedings, Sixth American Peptide Symposium, Georgetown University, E Gross, J Meienhofer (eds). Rockford, Illinois, Pierce Chemical 1979, pp 743–748

    Google Scholar 

  53. Simchowitz L, Spilberg I: Generation of superoxide radicals by human peripheral neutrophils activated by chemotactic factor. Evidence for the role of calcium. J Lab Clin Med 93:538, 1979

    Google Scholar 

  54. Bradford PG, Rubin RP: Pertussis toxin inhibits chemotactic factor-induced phospholipase C stimulation and lysomal enzyme secretion in rabbit neutrophils. FEBS Lett 183:317–320, 1985

    PubMed  Google Scholar 

  55. Okajima F, Ui M: 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, 1984

    PubMed  Google Scholar 

  56. Naccache PH, Molski TFP, Bargeat P, White JR, Sha'afi RI: Phorbol esters inhibit the f-Met-Leu-Phe and leukotriene B4-stimulated calcium mobilization and enzyme secretion in rabbit neutrophils. J Biol Chem 260:2125–2131, 1985

    PubMed  Google Scholar 

  57. Bokoch GM, Reed PW: Stimulation of arachidonic acid metabolism in the polymorphonuclear leukocyte by anN-formylated peptide. J Biol Chem 255:10,223–10,226, 1980

    Google Scholar 

  58. O'Flaherty JT: Neutrophil degranulation: Evidence pertaining to its mediation by combined effects of leukotriene B4, platelet-activating factor and 5-HETE. J Cell Physiol 122:229–239, 1985

    PubMed  Google Scholar 

  59. Palmblad J, Gyllenhammer H, Lindgren JA, Malmsten Cl: Effects of leukotrienes and f-Met-Leu-Phe on oxidative metabolism of neutrophils and eosinophils. J Immunol 132:3041–3045, 1984

    PubMed  Google Scholar 

  60. Beckman JK, Gay JC, Brash AR, Lukens JN, Oates JA: Stimulation by lipoxygenase products of superoxide anion production in FMLP-treated neutrophils. Lipids 20:318–321, 1985

    PubMed  Google Scholar 

  61. Feinmark SJ, Uden AM, Palmblad J, Malmsten C: Leukotriene biosynthesis by polymorphonuclear leukocytes from two patients with chronic granulomatous disease. J Clin Invest 72:1839–1843, 1983

    PubMed  Google Scholar 

  62. Beckman JK, Gay JC, Brash AR, Lukens JN, Oates JA: Differential effects of lipoxygenase products on FMLP and LTB4 evoked neutrophil aggregation. Lipids 20:357–360, 1985

    PubMed  Google Scholar 

  63. Goldman DW, Goetzl EJ: Heterogeneity of human polymorphonuclear leukocyte receptors for leukotriene B4. Identification of a subset of high affinity receptors that transduce the chemotactic response. J Exp Med 159:1027–1041, 1984

    PubMed  Google Scholar 

  64. Goetzl EJ, Burrall BA, Baud L, Scriven KH, Levine JD, Koo CH: Generation and recognition of leukotriene mediators of hypersensitivity and inflammation. Dig Dis Sci 33:xxx-xxx, 1988 (suppl)

    Google Scholar 

  65. Clancy RM, Dahinden CA, Hugh TE: Arachidonate metabolism by human polymorphonuclear leukocytes stimulated byN-formyl-Met-Leu-Phe or complement component C5a is independent of phospholipase activation. Proc Natl Acad Sci USA 80:7200–7204, 1983

    PubMed  Google Scholar 

  66. Salari H, Braquet P, Naccache P, Borglat P: Characterization of effect ofN-formyl-methionyl-leucyl-phenylalinine on leukotriene synthesis in human polymorphonuclear leukocytes. Inflammation 9:127–138, 1985

    PubMed  Google Scholar 

  67. Jubiz W, Radmark O, Malmsten C, Hansson G, Lindgren JA, Palglad JA, Uden AM, Samuelsson B: A novel leukotriene produced by stimulation of leukocytes with formyl-methionyl-leucyl-phenylalanine. J Biol Chem 257:6106–6110, 1982

    PubMed  Google Scholar 

  68. Hansson G, Radmark O: Leukotriene C4: Isolation from human polymorphonuclear leukocytes. FEBS Lett 122:87–90, 1980

    PubMed  Google Scholar 

  69. Goetzl EJ, Brindley LL, Goldman DW: Enhancement of human neutrophil adherence by synthetic leukotriene constituents of the slow-reacting substance of anaphylaxis. Immunology 50:35–41, 1983

    PubMed  Google Scholar 

  70. Naccache PH, Showell HJ, Becker EL, Sha'afi RI: Arachidonic acid induced degranulation of rabbit peritoneal neutrophils. Biochem Biophys Res Commun 87:292–299, 1979

    PubMed  Google Scholar 

  71. Volpi M, Naccache PH, Sha'afi RI: Arachidonate metabolite(s) increase the permeability of the plasma membrane of the neutrophils to calcium. Biochem Biophys Res Commun 92:1231–1237, 1980

    PubMed  Google Scholar 

  72. Ranney DF: Targeted modulation of acute inflammation. Science 227:182–184, 1985

    PubMed  Google Scholar 

  73. Chester JF, Ross JS, Malt RA, Weitzman SA: Acute colitis produced by chemotactic peptides in rats and mice. Am J Pathol 121:284–290, 1985

    PubMed  Google Scholar 

  74. Zipser RD, Patterson JB, LeDuc LE: Chemotactic peptide stimulation of leukotrienes from healthy and inflamed rabbit colons. J Pharmacol Exp Ther 241:218–222, 1987

    PubMed  Google Scholar 

  75. LeDuc LE, Zipser RD: Sites of eicosanoid production in healthy colons and experimental colitis. Gastroenterology 92:1496, 1987 (abstract)

    Google Scholar 

  76. Pearson AD, Eastman EJ, Laker MF, Craft AW, Nelson R: Intestinal permeability in children with Crohn's disease and coeliac disease. Br Med J (Clin Res) 285:20–21, 1982

    Google Scholar 

  77. Bjarnoson I, O'Morain C, Levi AJ, Peters TJ: Absorption of 51-chromium-labelled ethylenediaminetetracetate in inflammatory bowel disease. Gastroenterology 85:318–322, 1983

    PubMed  Google Scholar 

  78. Ukabam SO, Clamp JR, Cooper BT: Abnormal small intestinal permeability to sugars in patients with Crohn's disease of the terminal ilium and colon. Digestion 27:70–74, 1983

    PubMed  Google Scholar 

  79. Hollander D, Vadheim CM, Brettholz E, Petersen GM, Delahunty T, Rotter JI: Increased intestinal permeability in patients with Crohn's disease and their relatives. A possible etiologic factor. Ann Intern Med 105:883–885, 1986

    PubMed  Google Scholar 

  80. Podolsky DK, Isselbacher KJ: Composition of human colonic mucin. Selective alteration in inflammatory bowel disease. J Clin Invest 72:142–153, 1983

    PubMed  Google Scholar 

  81. Grisham MB, Granger DN: Neutrophil-mediated mucosal injury: Role of reactive oxygen metabolites. Dig Dis Sci 33:xxx-xxx, 1988 (suppl)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Division of Gastroenterology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, California

    Cynthia C. Nast MD & Louise E. LeDuc PhD

  2. Los Angeles, School of Medicine, University of California, Los Angeles, California

    Cynthia C. Nast MD & Louise E. LeDuc PhD

Authors
  1. Cynthia C. Nast MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Louise E. LeDuc PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by grants from the National Institutes of Health (AM 36200 and DK 36869).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nast, C.C., LeDuc, L.E. Chemotactic peptides. Digest Dis Sci 33 (Suppl 3), 50S–57S (1988). https://doi.org/10.1007/BF01538131

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01538131

Key words

Search

Navigation