title: Endotoxins affect diverse biological activity of chitosans in matters of hemocompatibility and cytocompatibility.
abstract: Chitosan is used in several pharmaceutical and medical applications, owing to its good cytocompatibility and hemocompatibility. However, there are conflicting reports regarding the biological activities of chitosan with some studies reporting anti-inflammatory properties while others report pro-inflammatory properties. In this regards we analyzed the endotoxin content in five different chitosans and examined these chitosans with their different deacetylation degrees for their hemocompatibility and cytocompatibility. Therefore, we incubated primary human endothelial cells or whole blood with different chitosan concentrations and studied the protein and mRNA expression of different inflammatory markers or cytokines. Our data indicate a correlation of the endotoxin content and cytokine up-regulation in whole blood for Poly-Morpho-Nuclear (PMN)-Elastase, soluble terminal complement complex SC5b-9, complement component C5/C5a, granulocyte colony-stimulating factor, Interleukin-8 (IL), IL-10, IL-13, IL-17E, Il-32α and monocyte chemotactic protein-1. In contrast, the incubation of low endotoxin containing chitosans with primary endothelial cells resulted in increased expression of E-selectin, intercellular adhesion molecule-1, vascular cell adhesion protein-1, IL-1β, IL-6 and IL-8 in endothelial cells. We suggest that the endotoxin content in chitosan plays a major role in the biological activity of chitosan. Therefore, we strongly recommend analysis of the endotoxin concentration in chitosan, before further determining if it has pro- or anti-inflammatory properties or if it is applicable for pharmaceutical and medical fields.
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University Hospital Tuebingen, University of Tuebingen, Calwerstr. 7/1, 72076, Tübingen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Nolte
authors.forename: Susanne
authors.initials: S
authors.lastname: Hossfeld
authors.forename: Marcell
authors.initials: M
authors.lastname: Post
authors.forename: Jan
authors.initials: J
authors.lastname: Niederlaender
authors.forename: Tobias
authors.initials: T
authors.lastname: Walker
authors.forename: Christian
authors.initials: C
authors.lastname: Schlensak
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Wendel
mesh_terms: D001672:Biocompatible Materials; D001769:Blood; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D048271:Chitosan; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans
chemical_list: D001672:Biocompatible Materials; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004731:Endotoxins; D048271:Chitosan