Abstract
Altered peripheral neutrophil function is a feature of IBD that may contribute to the chronicity and extragastrointestinal manifestations of this disease, but clinical evidence for such alterations is confounded by variations in patient characteristics, disease onset, and use of therapeutics that can influence neutrophil function. The use of a rat model of colitis has permitted us to characterize, in a controlled manner, the causal relationship between colitis and altered peripheral neutrophil function. At various times after induction of colitis with trinitrobenzene sulfonic acid (TNBS), peripheral neutrophils were isolated and assays of phagocytosis, chemotaxis, leukotriene B4 (LTB4) synthesis, and superoxide production were performed using a variety of stimuli. Circulating neutrophil numbers increased about fourfold within 12 hr of TNBS administration and returned to normal levels over the following two weeks. LTB4 synthesis in response to calcium ionophore decreased at 12 hr after induction of colitis, then returned to control levels. The chemotactic responses of peripheral neutrophils to LTB4 and FMLPin vitro and to LTB4 and IL-8in vivo were profoundly suppressed through the two-week study period. Phagocytosis of nitroblue tetrazolium was significantly enhanced (ca. threefold) at 12 hr after induction of colitis and remained elevated throughout the study period. Superoxide production was also significantly elevated in the early phase of colitis (by ca. fourfold), but was not different from control levels at seven and 14 days. These results demonstrate that colonic inflammation profoundly influences peripheral blood neutrophil function, although the direction and magnitude of the alteration varied among the various functions assessed. The prolonged depression of chemotactic activity may represent a physiological reaction to limit the inflammatory response.
Similar content being viewed by others
References
Hermanowicz A, Gibson PR, Jewell DP: The role of phagocytes in inflammatory bowel disease. Clin Sci 69:241–249, 1985
Anton PA, Targan SR, Shanahan F: Increased neutrophil receptors for and response to the proinflammatory bacterial peptide formyl-methionyl-leucyl-phenylalanine in Crohn's disease. Gastroenterology 97:20–28, 1989
Wallace JL, Higa A, McKnight GW, MacIntyre DE: Prevention and reversal of experimental colitis by a monoclonal antibody which inhibits leukocyte adherence. Inflammation 16:343–354, 1992
Curran FT, Keighley MRB: Neutrophil motility in Crohn's disease. Digestion 48:104–112, 1991
Williams JG, Hughes LE, Hallett MB: Toxic oxygen metabolite production by circulating phagocytic cells in inflammatory bowel disease. Gut 31:187–193, 1990
Wandall JH, Binder V: Leucocyte function in Crohn's disease. Gut 23:173–180, 1982
Curran FT, Allan RN, Keighley MRB: Superoxide production by Crohn's disease neutrophils. Gut 32:399–402, 1991
Elmgreen J, Binder V: The chemotactic function of neutrophils in ulcerative colitis. Scand J Gastroenterol 17:561–564, 1982
Couper R, Kapelushnik J, Griffiths AM: Neutrophil dysfunction in glycogen storage disease 1b: Association with Crohn's-like colitis. Gastroenterology 100:549–554, 1991
Ament ME, Ochs HD: Gastrointestinal manifestations of chronic granulomatous disease. N Engl J Med 288:382–387, 1973
Morris GP, Beck PL, Herridge MS, Depew W, Szewczuk MR, Wallace JL: Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803, 1989
Wallace JL, Kennan CM: An orally active inhibitor of leukotriene synthesis accelerates healing in a rat model of colitis. Am J Physiol 258:G527-G534, 1990
Carter L, Ferrari JK, Davison JS, Befus AD: Inhibition of neutrophil chemotaxis and activation following decentralization of the superior cervical ganglia. J Leukocyte Biol 51:597–602, 1992
Wallace JL, MacNaughton WK, Morris GP, Beck PL: Inhibition of leukotriene synthesis markedly accelerates healing in a rat model of inflammatory bowel disease. Gastroenterology 96:29–36, 1989
Woodman RC, Erickson RW, Rae J, Jaffe HS, Curnutte JT: Prolonged recombinant interferon-γ therapy in chronic granulomatous disease: evidence against enhanced neutrophil oxidase. Blood 79:1558–1563, 1992
Bradley PP, Priebat DA, Christensen RD, Rothstein G: Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206–209, 1982
Ward M, Eastwood MA: The nitroblue tetrazolium test in Crohn's disease and ulcerative colitis. Digestion 14:179–193, 1976
Kirk AP, Cason J, Fordham NJ, Brown KA, Goddard DH, Holbrow EJ, Lennard-Jones JE: Polymorphonuclear leukocyte function in ulcerative colitis and Crohn's disease. Dig Dis Sci 28:236–278, 1983
Cole AT, Garlick N, Buchanan M, Galvin A, Hawkey CJ, Robins A: Reduced expression of neutrophil neutral endopeptidase in inflammatory bowel disease. Gastroenterology 106:A666, 1994
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Carter, L., Wallace, J.L. Alterations in rat peripheral blood neutrophil function as a consequence of colitis. Digest Dis Sci 40, 192–197 (1995). https://doi.org/10.1007/BF02063966
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02063966