| Selectin-mediated leukocyte rolling along the endothelium is of key important mechanism for maintaining the cellular immune response. Heparin, a commonly used anticoagulant in the clinic, can function as a ligand for P-selectin and can block P-selectin binding to its nature carbohydrate ligands. The anti-inflammatory activities of heparin have partly been related to inhibition of P-selectin binding. Chitin/Chitosan is an abundant natural amino-polysaccharides, which have excellent biological functional properties, biocompatibility, biodegradability, non-toxicity, adsorption properties, etc. Chitin and chitosan sulphates as a kind of heparinoids possess many bioactivities such as anticoagulant, anti-metastasis, antivirus activities, etc.In this study, we prepared 6 chitin/chitosan derivatives by means of selective chemical modification. IR and NMR were performed to identify the structure of all derivatives. We also selected the human promyeloid HL-60 cells and CHO cells of expressing P-selectin by stably transfected human P-selectin cDNA to analyze the inhibitory effect of heparin and chitin/chitosan heparinoids to the interaction of these two cell line under static and shear flow conditions.The results indicate that the structures of six derivatives are just as desired. The inhibitory activity results show that N,6-S-Chitosan, N,3,6-S-Chitosan and 3,6-S-CM-Chitin exhibit excellent inhibitory ability to the binding of the HL60 and CHO-P cell under static and flow conditions. And the inhibitory ability of these three derivatives are exceeded the heparin activities. However, the other three derivatives exhibit little affects.This study is the first time to utilize natural abundant chitin/chitosan as the fundamental materials targeting to P-selectin, one of the key proteins during the recruitment of leukocytes from the blood into tissues. In conclusion, our study will provide a valuable experimental foundation for clinical trial of anti-inflammation.
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