|Kehrli, Jr, Marcus|
Submitted to: Microbial Pathogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/26/2000
Publication Date: N/A
Citation: Interpretive Summary: Some of the spiral-shaped bacteria which can infect the intestinal tract are known as intestinal spirochetes. These intestinal spirochetes cause dysentery in swine or intestinal disease in other animals. In response to infection of the intestinal tract by these intestinal spirochetes, certain types of white blood cells are called upon. These cells are found at sites sof infection in the gut. In the present study, we used antibodies to proteins on the surface of these cells to reduce the number of these white blood cells in the intestine. This treatment resulted in fewer of these white blood cells in the gut. In addition, there was less evidence of intestinal disease in affected animals. We also showed how important these white blood cells are to the disease process, in that reducing their numbers through the use of another antibody also resulted in less severe disease. Therefore, treatment of animals with these antibodies could be used as a therapy for treating these types of intestinal diseases.
Technical Abstract: Colitis develops in mice infected with the spirochete Brachyspira (Serpulina) hyodysenteriae. Numerous polymorphonuclear leukocytes (PMNs) are seen in the cecal lamina propria and submucosa 24 to 48 h postinfection. To assess the role of PMNs in colitis, we utilized mAbs specific for beta 1 (CD29) or beta 2 (CD18) integrins to block PMN recruitment into the inflamed gut. Macroscopic lesions were less severe in mice treated with either mAb compared to lesions observed in isotype control-treated mice. While these mAbs may inhibit extravasation of other leukocytes, the central role of PMNs was further demonstrated in that the acute colitis was less severe following neutrophil depletion. There was less mucosal edema and epithelial erosions in ceca of mice which received anti-Ly6G, -CD18 or -CD29 mAb compared to mice receiving control mAb. Moreover, there was a significant reduction in PMN infiltration in ceca of mice treated with anti-CD18. The reduction in infiltrating PMNs did not result from inhibition of CXC chemokines as demonstrated by expression of MIP-2 mRNA in ceca of mice treated with anti-CD18. In contrast, there was no significant reduction in PMN infiltration in mice treated with anti- CD29, suggesting that PMN recruitment into the inflamed intestine was CD29- independent. It is noteworthy that the number of PMNs seen in anti-CD18- treated mice was significantly higher than was observed in non-infected mice. Thus, these results provide evidence for a threshold number of PMNs necessary for acute lesion development and indicate that CD18, but not CD29, adhesive pathways are crucial for PMN recruitment in acute colitis.