Avaliação do papel de mastócitos na imunopatologia do megacólon chagásico, com ênfase na sua interação com neurônios e eosinófilos

Abstract

Megacolon is the most frequently observed complication among individuals who develop the digestive clinical form of Chagas disease. Patients present dilation of the rectum-sigmoid portion and motility disorders, due to the denervation process. Increasing of mast cell (MCs) and eosinophil numbers are constantly observed in the dilated colon, which suggests a role for those cells in such pathology. Besides, the numbers of tryptase-immunoreactive (IR) MCs are negatively correlated with the area of nerve fibers expressing PGP 9.5 or vasoactive intestinal polypeptide (VIP-IR), an anti-inflammatory neuromediator. On view of those data, we suggest that tryptase-IR MCs could play a role in the chronic infection associated inflammation and denervation process. Tryptase is a protease that cleaves the protease-activated receptor type 2 (PAR2) on the surface of inflammatory cells and neurons, inducing the production of pro-inflammatory cytokines, leukocyte recruitment, specially eosinophils, and neuronal activation and death. Here we demonstrated the expression of PAR2 by neurons, confirming data from the literature. In colon of patients with megacolon, we observed increased numbers of tryptase-IR or chymase-IR MCs, being most of them with signs of activation (piecemeal or anaphylactic degranulation), and some in close proximity (less than 5 um) to neurons. Besides, we observed a positive correlation between numbers of tryptase-IR MCs and eosinophils, and increased numbers of PAR2-IR eosinophils in colon of patients with megacolon. In conjunction with data from the literature, the results presented here suggest a role for tryptase-IR MCs in eosinophil activation and recruitment, in the denervation process and, consequently, in the development of megacolon.