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Published online before print April 4, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0904541

Received for publication September 21, 2004.
Revised February 24, 2005.
Accepted for publication March 4, 2005.

Article

Local and systemic activity of the polysaccharide chitosan at lymphoid tissues after oral administration

Carina Porporatto ^*, Ismael D. Bianco , and Silvia G. Correa ^*@

*Inmunología, CIBICI (CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Argentina; and Centro de Excelencia en Productos y Procesos de la Provincia de Córdoba (CEPROCOR), Agencia Córdoba Ciencia S.E. and CONICET, Argentina

^@ To whom correspondence should be addressed. E-mail: scorrea{at}bioclin.fcq.unc.edu.ar.

	Abstract

Chitosan is a cationic polysaccharide derived from the partial deacetylation of chitin, which exhibits particular properties: interacts with negatively charged sites on the cell surface; changes the permeability of intestinal epithelium, enhancing the uptake of peptides and proteins; and activates leukocytes. Antigens coadministered or encapsulated with the polysaccharide show improved mucosal and systemic humoral immune responses, although the mechanism is poorly understood. Herein, we characterized in Peyer’s patches mesenteric lymph nodes and spleen molecular events triggered after oral administration of chitosan in the absence of protein antigen. Sixteen hours after feeding, we studied the uptake and distribution of the polysaccharide, the phenotype of recruited antigen-presenting cells (APC), the induction of cytokines such as tumor necrosis factor , interleukin (IL)-12, IL-4, IL-10, and transforming growth factor- (TGF-), and the activation of T lymphocytes. We show here that the uptake of chitosan at inductive mucosal sites involves CD11b/c+ APC and that chitosan feeding increases the percentage of OX62+ dendritic cells, which up-regulate the major histocompatibility complex class II antigens without changing the expression of costimulatory CD80 or CD86 molecules. The polysaccharide elicits the release of IL-10 as well as the expression of IL-4 and TGF- in mucosa, and in spleen, the activation of CD3+ T cells occurs. Our results demonstrate that chitosan acts by enhancing the T helper cell type 2 (Th2)/Th3 microenvironment in the mucosa. A single dose of this polysaccharide exhibits local and systemic effects, and its activity could be relevant in the maintenance of the intestinal homeostasis.

Key Words: mucosa • immature dendritic cell • cytokines