Ability of the polysaccharide chitosan to inhibit proliferation of CD4+ lymphocytes from mucosal inductive sites, in vitro and in vivo

PORPORATTO C; CANALI M.M.; BIANCO I.D.; CORREA S.G.

CELL PROLIFERATION

WILEY-BLACKWELL PUBLISHING, INC

Año: 2009 vol. 42 p. 780 - 787

0960-7722

Abstract. Objective: After oral administration of chitosan, a copolymer of glucosamine and N-acetylglucosamine, mesenteric lymph node (MLN) lymphocytes exhibit traits of anergy, a process coupled with the inability of a mature T cell to proliferate. We wondered whether the biological activity of chitosan could be affecting the division of lymphocytes at the mucosal inductive sites. Materials & methods:  We studied the effect of chitosan on the proliferation of carboxyfluorescein diacetate (CFSE)-labeled MLN lymphocytes stimulated with concanavalin A (ConA) in vitro. We assessed the expression of CD25 and CD71 activation markers and the pro-apoptotic molecule CD95L. Moreover, we studied the effect ex vivo, in CFSE labeled MLN cells isolated after feeding single or repetitive doses of the polysaccharide and we evaluated the cell cycle. Results: Chitosan suppressed the proliferation and downmodulated the expression of the CD25 molecule in MLN CD4+ cells isolated from normal rats. After in vivo contact, chitosan inhibited the proliferation of MLN cells and reduced the secretion of IFN-γ.  Furthermore, the sustained feeding produced a reduction in the percentage of CD4+ cells in the S phase of the cell cycle. Conclusion: Herein, we demonstrate the ability of chitosan to suppress in vivo and in vitro the proliferation of CD4+ lymphocytes from mucosal inductive sites. This effect could be relevant in the modulatory activity of chitosan in the intestinal microenvironment.