THE PRESENCE OF PEPTIDOGLYCAN POLYSACCHARIDE COMPLEXES IN THE BOWEL WALL AND THE CELLULAR-RESPONSES TO THESE COMPLEXES IN CROHNS-DISEASE

Interestingly, using a monoclonal antibody, peptidoglycan-polysacchari de complexes (PPC) were detected intracellularly in the mucosa and sub mucosa of the bowel wall of Crohn's disease (CD) patients. PPC are the main constituents of the gram-positive bacterial cell wall. These PPC were however detected in the normal bowel wall also. Therefore, in th is study the hypothesis that an enhanced immune responsiveness to bact erial antigens plays a pivotal role in the induction or the chronicity of CD was tested. As antigens, the peptidoglycan structures of intest inal bacteria (Eubacterium aerofaciens or fecal PPC) or of Streptococc us pyogenes, the 65-kDa heat shock protein and muramyl dipeptide (MDP) , the smallest bioactive subunit of peptidoglycan, were used. The prol iferative responses of peripheral blood (PB) mononuclear cells (MNC) o f healthy subjects and patients in a remissive stage of CD or an activ e CD stage were examined. Of this last patient group the MNC responses of the mesenterial lymph nodes that drain the inflamed gut area were measured also. The responses of PB-MNC of the healthy subjects and the patients in a remissive CD stage were not different. Compared to the responses in remissive CD, the PB-MNC responses in active CD to the eu bacterial cell wall and streptococcal cell wall antigen were significa ntly higher. At the inflammation site in active CD, the lymph nodes, t he responses to most of the bacterial antigens were significantly high er than in the PB. In summary, the results show the presence of bacter ial peptidoglycan in the bowel wall and the immune responsiveness, esp ecially at the inflammation site, to these antigens in active CD and t herefore present suggestive evidence for the role of peptidoglycan in the etiology and/or pathogenesis of CD. (C) 1994 Academic Press, Inc.