Abstract
Phagocytic, chemotactic, and oxidative metabolic capacity of circulating neurtrophils was studied in 20 patients with Crohn's disease.In vitro tests of chemotaxis and phagocytosis of isolated neutrophils from patients did not differ from that of healthy controls. However, superoxide anion production by phorbol-myristate-acetate and formylmethionyl-leucylphenylalanine-stimulated neutrophils from patients with Crohn's disease was significantly diminished compared with controls. Measurement of cytochromeb 559 in total membranes of neutrophils from patients showed that it was significantly lower than in controls. Disease activity did not correlate either with the production of superoxide anion or with the cytochromeb 559 content. It is concluded that oxidative metabolism is impaired in neutrophils from patients with Crohn's disease and that this defect could be caused by a reduced content in membraneb-type cytochrome. Although this defective neutrophil function may contribute to granuloma formation, other factors have to be implicated in disease inflammatory activity.
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References
Adams DO: The granulomatous inflammatory response. Am J Pathol 84:164–191, 1976
Smith RM, Curnutte JT: Molecular basis of chronic granulomatous disease. Blood 77:673–686, 1991
Wandall JH, Binder V: Leucocyte function in Crohn's disease. Studies on mobilisation using a quantitative skin window technique and on the function of circulating polymorphonuclear leucocytesin vivo. Gut 23:173–180, 1982
Morain CO, Segal AA, Walker D, Levi AJ: Abnormalities of neutrophil function do not cause the migration defect in Crohn's disease. Gut 22:817–822, 1981
Worsaae N, Staehr-Johansen K, Christensen KC: Impairedin vitro function of neutrophils in Crohn's disease. Scand J Gastroenterol 17:91–96, 1982
Curran FT, Youngs DJ, Allan RN, Keighley MRB: Candidacidal activity of Crohn's disease neutrophils. Gut 32:55–60, 1991
Best WR, Becktel JM, Singleton JW, Kern F: Development of a Crohn's disease activity index (National Cooperative Crohn's Disease Study). Gastroenterology 70:439–444, 1976
Böyum A: Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest (suppl 97) 21:77–89; 1986
Balsinde J, Diez E, Schüller A, Mollinedo F Phospholipase A2 activity in resting and activated human neutrophils. Substrate specificity, pH dependence and subcellular localization. J Biol Chem 263:1929–1936, 1988
Koch C: Acquired defect in the bactericidal function of neutrophil granulocytes during bacterial infections. Acta Pathol Microbiol Scand (Sect B) 82:439–447, 1974
Boyden SV: The chemotactic effect of mixture of antibody and antigen on polymorphonuclear leukocytes. J Exp Med 115:453–466, 1962
Balsinde J, Mollinedo F: Specific activation by concanavalin A of the superoxide anion generation capacity during U937 differentiation. Biochem Biophys Res Commum 151:802–808, 1988
Cross AR, Higson FK, Jones OTG, Harper AM, Segal AW: The enzymic reduction and kinetics of oxidation of cytochromeb 245 of neutrophils. Biochem J 204:479–485, 1982
Berton G, Cassatella MA, Bellavite P, Rossi F: Molecular basis of macrophage activation. Expression of the low potential cytochromeb and its reduction upon cell stimulation in activated macrophages. J Immunol 136:1393–1399, 1986
Andrew PW, Robertson AK, Lowrie DB, Cross AR, Jones OTG: Induction of synthesis of components of the hydrogen peroxide-generating oxidase during activation of the human monocytic cell line U937 by interferon γ. Biochem J 248:281–283, 1987
Capeillere-Blandin C, Masson A, Descamps-Latscha B: Molecular characteristic of cytochrome b558 isolated from human granulocytes, monocytes and HL60 and U937 cells differentiated, into monocyte/macrophages. Biochim Biophys Acta 1094:55–65 1991
Bainton DF, Ullyot JL, Farquhar MG: The development of neutrophilic polymorphonuclear leukocytes in human bone marrow. J Exp Med 166:1641–1653, 1971
Sloan EP, Crawford DR, Schneider DL: Isolation of plasma membrane from human neutrophils and determination of cytochromeb and quinone content. J Exp Med 153:1316–1328, 1981
Ohno Y, Seligmann BE, Gallin JI: Cytochromeb translocation to human plasma membranes and superoxide release. Differential effects ofN-formylmethionylleucylphenylalanine, phorbol myristate acetate and A23187. J Biol Chem 260:2409–2414, 1985
Parkos CA, Cochrane CG, Schmitt M, Jesaitis AJ: Regulation of the oxidative response of human granulocytes to chemoattractants: No evidence for stimulated traffic of redox enzymes between endo and plasma membranes. J Biol Chem 260:6541–6547, 1985
Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principles of dying binding. Anal Biochem 72:224–254, 1976
Rohdes JM, Jewell DP: Motility of neutrophils and monocytes in Crohn's disease and ulcerative colitis. Gut 24:73–77, 1983
D'Amelio R, Rossi P, Le Moli S, Ricci R, Montano S, Pallone F:In vitro studies on cellular and humoral chemotaxis in Crohn's disease using the under agarose gel technique. Gut 22:566–570, 1981
Hermanowicz A, Gibson PR, Jewell JP: The role of phagocytes in inflammatory bowel disease. Clin Sci 69:241–249, 1985
Verspaget HW, Mieremet-Ooms MAC, Weterman IT, Peña AS: Partial defect of neutrophil oxidative metabolism in Crohn's disease. Gut 25:849–853, 1984
Verspaget HW, Elmgreen J, Weterman IT, Peña AS, Riis P, Lamers CBHW: Impaired activation of the neutrophil oxidative metabolism in chronic inflammatory bowel disease. Scan J Gastroenterol 21:1124–1130, 1986
Verspaget HW, Peña AS, Weterman IT, Lamers CBHW: Diminished neutrophil function in Crohn's disease and ulcerative colitis identified by decreased oxidative metabolism and low superoxide dismutase content. Gut 29:223–228, 1988
Curran FT, Allan RN, Keighley MRB: Superoxide production by Crohn's disease neutrophils. Gut 32:399–402, 1991
Morel F, Doussiere J, Vignais PV: The superoxidegenerating oxidase of phagocytic cells. Physiological, molecular and pathological aspects. Eur J Biochem 201:523–546, 1991
Segal AW: Absence of both cytochromeb −245 subunits from neutrophils in X-linked chronic granulomatous disease. Nature 326:88–91, 1987
Parkos CA, Allen RA, Cochrane CG, Jesaitis AJ: Purified cytochromeb from human granulocyte plasma membrane is comprised of two polypeptides with relative molecular weights 91,000 and 22,000. J Clin Invest 80:732–742, 1987
Ament ME, Ochs DH: Gastrointestinal manifestations of chronic granulomatous disease N Engl J Med 288:382–387, 1973
Werlin SL, Chusid J, Caya J, Oechler HW: Colitis in chronic granulomatous disease. Gastroenterology 82:328–331, 1982
Couper R, Kapelushnik J, Griffiths AM: Neutrophil dysfunction in glycogen storage disease Ib. Association with Crohn's-like colitis. Gastroenterology 100:549–554, 1991
Fantone JC, Ward PA: Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol 107:397–418, 1982
Larsen GL, Henson PM: Mediators of inflammation. Annu Rev Immunol 1:335–359, 1983
Halliwell B, Gutteridge JMC: Oxygen toxicity, oxygen radicale, transition metals and disease. Biochem J 219:1–14, 1984
Fox HB, De Togni P, Babior BM: Phagocytes and carcinogenesis. Immunol Today 6:327–328, 1985
Weiss SJ: Tissue destruction by neutrophils. N Engl J Med 320:365–376, 1989
James SP, Fiocchi C, Graeff AS, Strober W: Phenotypic analysis of lamina propria lymphocytes. Predominance of helper-inducer and cytolytic T-cell phenotypes and deficiency of suppressor-inducer phenotypes in Crohn's disease and control patients. Gastroenterology 91:1486–1489, 1986
James SP: Remission of Crohn's disease after human immunodeficiency virus infection. Gastroenterology 95:1667–1669, 1988
James SP, Strober W, Quinn TC, Danovitch SH: Crohn's disease. New concepts of pathogenesis and current approaches to treatment. Dig Dis Sci 32:1297–1310, 1987
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This work was supported by grants 87/1180 and 88/1549 from the Fondo de Investigaciones Sanitarias de la Seguridad Social, Spain.
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Solis-Herruzo, J.A., Fernandez, B., Vilalta-Castell, E. et al. Diminished cytochromeb content and toxic oxygen metabolite production in circulating neutrophils from patients with Crohn's disease. Digest Dis Sci 38, 1631–1637 (1993). https://doi.org/10.1007/BF01303171
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DOI: https://doi.org/10.1007/BF01303171