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

OBJECTIVE

After oral administration of chitosan (a copolymer of glucosamine and N-acetylglucosamine), mesenteric lymph node (MLN) lymphocytes exhibited traits of anergy, a process coupled with inability of mature T cells to proliferate. We wondered whether biological activity of chitosan could be affecting division of lymphocytes at the mucosal inductive sites.

MATERIALS AND METHODS

We studied the effect of chitosan on proliferation of carboxyfluorescein diacetate-labelled MLN lymphocytes stimulated with concanavalin A in vitro. We assessed expression of CD25 and CD71 activation markers and pro-apoptotic molecule CD95L. Moreover, we studied the effect of chitosan ex vivo, in carboxyfluorescein diacetate-labelled MLN cells isolated after feeding single or repetitive doses of the polysaccharide, and we evaluated cell cycle parameters.

RESULTS

Chitosan suppressed cell proliferation and down-modulated expression of CD25 in these MLN CD4+ cells isolated from normal rats. After in vivo contact, chitosan inhibited proliferation of MLN cells and reduced secretion of interferon-gamma. Furthermore, sustained feeding produced reduction in percentage of CD4+ cells in S phase of the cell cycle.

CONCLUSION

Here we demonstrate the ability of chitosan to suppress proliferation of CD4+ lymphocytes from mucosal inductive sites in vivo and in vitro This effect could be relevant in modulatory activity of chitosan in the intestinal microenvironment.