Original article
Regulation of neutrophils in ulcerative colitis by colonic factors: A possible mechanism of neutrophil activation and tissue damage

https://doi.org/10.1016/S0022-2143(97)90109-8Get rights and content

Abstract

The mucosal injury of active ulcerative colitis (UC) could involve enhanced migration and activation of neutrophils (PMNs). Because, in vitro, PMNs from patients with UC appear normal and are not therefore a likely cause for the enhancements, we hypothesized an abnormal colonic milieu. We previously found that factors in the UC colonic milieu markedly increase production of reactive oxygen species (ROS) by control PMNs. We now hypothesize that these factors also regulate PMN surface integrins, that regulation of UC PMNs is different than that of control PMNs, and that the integrin regulation is consistent with the ROS regulation. Using rectal dialysis, we sampled the colonic milieu in patients with active UC, in patients with inactive UC, and in control subjects. We monitored a key PMN adhesion molecule, CD1lb. When control PMNs were tested, active UC rectal dialysate was almost as effective (+115%) as N-formyl-methionyl-leucyl-phenylalanine (+132%) in up-regulating CD 11b. When inactive UC PMNs were tested, baseline CD 11b was 50% higher than that for control PMNs. In contrast, rectal dialysates failed to up-regulate CD11b of inactive UC PMNs and in fact down-regulated CD11b. Preincubating control PMNs with UC rectal dialysates converted their CD11b response to PMN activators from up-regulation to down-regulation, mimicking inactive UC PMNs. Changes in intracellular calcium levels paralleled these changes in CD11b. Rectal dialysate-induced changes in both CD11b and calcium paralleled our previous findings on rectal dialysate-induced changes in ROS production. Thus the net overall effect of factors in the colonic milieu is a consistent and predictable regulation of PMN function—proinflammatory in UC, anti-inflammatory in control subjects. These factors may be a critical part of the pathophysiology of UC.

References (44)

  • JB Kirsner et al.

    Recent developments in nonspecific inflammatory bowel disease (second of two parts)

    N Engl J Med

    (1982)
  • RM McDonaldson
  • A Keshavarzian et al.

    Role of reactive oxygen metabolites in experimental colitis

    Gut

    (1990)
  • DA Parks et al.

    Role of oxygen-derived free radicals in digestive tract diseases

    Surgery

    (1983)
  • SJ Weiss

    Tissue destruction by neutrophils

    N Engl J Med

    (1989)
  • JG Williams et al.

    Effect of sulphasalazine and its active metabolite, 5-amino-salicylic acid, on toxic oxygen metabolite production by neutrophils

    Gut

    (1989)
  • A Keshavarzian et al.

    Granulocyte migration in uncomplicated intestinal anastomosis in man

    Dig Dis Sci

    (1986)
  • V Graves et al.

    Simultaneous mobilization of Mac-1 (CD11b/ CD18) and formyl peptide chemoattractant receptors in human neutrophils

    Blood

    (1992)
  • CW Smith et al.

    Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro

    J Clin Invest

    (1989)
  • JH Wandall

    Neutrophilic granulocyte function

  • TA Springer

    Adhesion receptors of the immune system

    Nature

    (1990)
  • RS Larson et al.

    Structure and function of leukocyte integrins

    Immunol Rev

    (1990)
  • Cited by (24)

    • Hydroalcoholic extract of Tagetes erecta L. flowers, rich in the carotenoid lutein, attenuates inflammatory cytokine secretion and improves the oxidative stress in an animal model of ulcerative colitis

      2019, Nutrition Research
      Citation Excerpt :

      MPO is a heme peroxidase, present mainly in the azurophil granules of neutrophils [41] and commonly used as an indirect marker of neutrophil migration. Intestinal neutrophil accumulation with increased MPO activity is common in patients with IBD, and results in animal models have also strengthened neutrophil’s contribution to intestinal damage in IBD [42-46]. As shown in Table 2, the DHETE-treated colitic group experienced a reduction in the activity of the MPO by 82% when compared to the colitic group treated with vehicle (17.6 ± 2.2 m DO/mg protein).

    • High-Fiber Diets in Gastrointestinal Tract Diseases

      2019, Dietary Interventions in Gastrointestinal Diseases: Foods, Nutrients, and Dietary Supplements
    View all citing articles on Scopus
    View full text