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Role of neutrophils in acetic acid-induced colitis in rats

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Abstract

Intrarectal administration of 4% acetic acid produces diffuse inflammation that ultimately results in erosions and ulcerations of the rat colon. Although this model of colitis has been used extensively over the past several years, there are no quantitative data available regarding the relationship between neutrophil infiltration and mucosal injury during times of active inflammation. Therefore, the objective of this study was to define the role of extravasated neutrophils as mediators of mucosal injury and inflammation in acetic acid-induced colitis. We found the intrarectal administration of 4% acetic acid produced an 11-fold increase in colonic mucosal permeability, a 9-fold increase in colonic MPO activity, and a 1.6-fold increase in colon weight at 48 h following administration of acetic acid. In addition, we found significant correlations between colonic MPO activity and mucosal permeability and between colonic MPO activity and colon weight (P < 0.01 for both). These data suggested that inflammatory neutrophils may mediate mucosal injury and inflammation in this model of colitis. To assess the role of circulating neutrophils, rats were rendered neutropenic for 48 h by the intraperitoneal administration of antiserum directed toward rat neutrophils (ANS). Although ANS treatment reduced both the number of circulating neutrophils and colonic MPO activity to less than 10% of control values, it did not attenuate the increases in colonic mucosal permeability nor did it attenuate the increases in colon weight produced by acetic acid. Histological inspection confirmed that ANS treatment was not effective in attenuating the injury to the epithelial barrier. These data demonstrate that infiltrating neutrophils do not mediate the mucosal injury and inflammation observed in acetic acid-induced colitis.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Louisiana State University Medical Center, 71130, Shreveport, Louisiana

    Tamaki Yamada, Barbara J. Zimmerman & Matthew B. Grisham

  2. Department of Cellular Biology and Anatomy, Louisiana State University Medical Center, 71130, Shreveport, Louisiana

    Robert D. Specian

Authors
  1. Tamaki Yamada
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  2. Barbara J. Zimmerman
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  3. Robert D. Specian
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  4. Matthew B. Grisham
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Additional information

This work was supported by grants from the NIH (DK39168), Crohn's and Colitis Foundation of America and Pharmacia LEO Therapeutics (Uppsala, Sweden).

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Yamada, T., Zimmerman, B.J., Specian, R.D. et al. Role of neutrophils in acetic acid-induced colitis in rats. Inflammation 15, 399–411 (1991). https://doi.org/10.1007/BF00917356

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