Another parameter that may modify the response of PMNs to chitosan is the form in which the chitosan is used. Vandevord and coworkers reported that a chitosan scaffold made Regorafenib mw with chitosan of 92% DDA is chemotactic for PMN in vivo. Because 92% DDA chitosan is structurally more similar to 95 M than to 80 M chitosan, our data indicate that PMN migration to 92% DDA chitosan should be quite modest. The discrep ancy between this previous observation and our findings could potentially be explained Inhibitors,Modulators,Libraries by the fact that the scaffold used in the in vivo study was prepared by coating polytetrafluoroethylene tubes with 92% DDA chitosan, and did not employ pure chi tosan. It will be of therapeutic interest to determine how differ ently PMNs react to chitosans of the same percentage DDA of different structural forms suspension versus scaffold.

It is generally accepted that PMN phagocytose chitosan, but no microscopy Inhibitors,Modulators,Libraries studies have been performed to demonstrate that PMNs indeed internalize chitosan. This is a relevant ques tion because PMNs can respond to foreign material without Inhibitors,Modulators,Libraries necessarily internalizing it. We provide direct evidence that PMNs can internalize 80 M chitosan without stimulating degranulation. Around 10% of PMNs internalized 80 M chi tosan, in the presence of 0. 5% heat inactivated serum. These observations are quite different to those in PMN and monoso dium urate crystals, which have a poor capacity for internaliza tion while strongly activating PMNs, probably because of an autocrine effect. It is highly likely that lipid mediators are involved in this autocrine effect.

In our internalization assay, PMNs readily internalized zymosan, a yeast cell wall prepara tion that activates neutrophils. Because both 95 M and 80 M were internalized Inhibitors,Modulators,Libraries without activating neutrophils, our data dem onstrate that internalization of a polysaccharide Inhibitors,Modulators,Libraries biomaterial does not automatically trigger degranulation. Recently, PMNs were reported to express the mannose recep tor, a receptor that is implicated in the internalization of chitosan by macrophages. We provide evidence that monocytes internalize 80 M chitosan more readily than PMNs, suggesting that the molecular mechanisms involved in the internalization of 80 M chitosan by PMNs differ from those of macrophages. This does not imply a less important role of PMNs in chitosan based wound healing. PMNs usually out number macrophages in certain phases of wound healing and can collectively synthesize large AZD9291 clinical quantities of soluble media tors. Conclusions In summary, 80 M chitosan is chemotactic for human PMNs but does not activate additional PMN effector functions such as degranulation and superoxide production.