Distribution of the interleukin-8 receptors, CXCR1 and CXCR2, in inflamed gut tissue

There is increasing evidence to suggest that the potent neutrophil chemoatt ractant interleukin-8 (IL-8) has an important role in the pathogenesis of i nflammatory bowel disease. IL-8 mediates its actions via two cell surface r eceptors, CXCR1 and CXCR2. This paper describes the distribution of these I L-8 receptors in the normal gastrointestinal tract and how this is modified in ulcerative colitis (UC). Paraffin-embedded colonic resection specimens were stained with monoclonal antibodies directed against CXCR1 and CXCR2 in ten cases of total UC, 16 cases of appendicitis, and 11 histologically nor mal sections. A semiquantitative scale of 0-4 was used to assess the propor tion and intensity of positively stained cells within certain defined areas of tissue. A comparative assessment was made of the distribution of variou s cell populations. Dual immunostaining was used to confirm the phenotype o f positively staining cells. In the histologically normal colon, the antibo dy against CXCR1 stained a subpopulation of macrophages deep to the epithel ium and germinal centre lymphocytes. A similar pattern of staining was seen in acute appendicitis, with in addition some positively stained neutrophil polymorphs. In UC, there was upregulation of CXCR1, with a striking increa se in positively stained macrophages throughout the mucosa and of B and T l ymphocytes outside the germinal centre areas. There was also intense upregu lation of CXCR1 expression by the luminal epithelium, reflected in the epit helial staining score (mean +/-SE = 1.8+/-44 for UC cases, vs. 0.23+/-0.16 for controls and 0.25+/-0.14 for acute appendicitis). CXCR2 was only expres sed on a small population of lamina propria mononuclear cells and crypt epi thelial cells, with no significant differences observed between the groups. These results suggest that IL-8 may, through CXCR1, have a role beyond neu trophil recruitment in mediating the immune response in UC and that this is not merely a consequence of the acute inflammation seen in UC. Copyright ( C) 2000 John Wiley & Sons, Ltd.