Park Chan J, Gabrielson Nathan P, Pack Daniel W, Jamison Russell D, Wagoner Johnson Amy J
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, 1304 W Green Street, Urbana, IL 61801, USA.
Biomaterials. 2009 Feb;30(4):436-44. doi: 10.1016/j.biomaterials.2008.09.060. Epub 2008 Oct 31.
Research interest in chitosan stems in part from the demonstrated wound healing properties. The benefits of chitosan as a therapeutic agent appear to be paradoxical because chitosan also elicits neutrophil infiltration indicative of an inflammatory response. While the affinity between chitosan and neutrophils has been well documented, the underlying mechanism is unclear. To our knowledge, no studies have investigated the consequences of chitosan-neutrophil interaction to explain neutrophil migration. To that end, transwell migration assays to chitosan of varying extent of acetylation were conducted using a differentiated model cell line (HL60-PMN) in order to assess the effect of chitosan chemistry and the resultant physical properties such as charge and hydrophobicity on neutrophil migration. As chitosan N-acetylation increased, neutrophil migration increased and chitosan became less positively charged and more hydrophobic. Moreover, HL60-PMN cells secreted the potent neutrophil chemokine IL-8, also known as CXCL8, when exposed to chitosan and IL-8 levels increased with N-acetylation, and migration was inhibited by anti-IL-8 antibodies. Collectively these results suggest that chitosan-neutrophil interaction is encouraged by material properties, results in IL-8 secretion, and causes migration of neutrophils to chitosan. The implication is that the wound healing properties of chitosan may be enhanced through the attenuation of overabundant neutrophils, and thus the inflammatory response, simply by changing chitosan N-acetylation.
对壳聚糖的研究兴趣部分源于其已被证实的伤口愈合特性。壳聚糖作为一种治疗剂的益处似乎自相矛盾，因为壳聚糖也会引发指示炎症反应的中性粒细胞浸润。虽然壳聚糖与中性粒细胞之间的亲和力已有充分记录，但其潜在机制尚不清楚。据我们所知，尚无研究调查壳聚糖 - 中性粒细胞相互作用的后果以解释中性粒细胞迁移。为此，使用分化的模型细胞系（HL60 - PMN）对不同乙酰化程度的壳聚糖进行了Transwell迁移试验，以评估壳聚糖化学性质以及由此产生的物理性质（如电荷和疏水性）对中性粒细胞迁移的影响。随着壳聚糖N - 乙酰化增加，中性粒细胞迁移增加，且壳聚糖的正电荷减少，疏水性增加。此外，HL60 - PMN细胞在暴露于壳聚糖时会分泌强效中性粒细胞趋化因子IL - 8（也称为CXCL8），且IL - 8水平随N - 乙酰化增加而升高，迁移受到抗IL - 8抗体的抑制。这些结果共同表明，壳聚糖 - 中性粒细胞相互作用受材料特性促进，导致IL - 8分泌，并引起中性粒细胞向壳聚糖迁移。这意味着，仅通过改变壳聚糖的N - 乙酰化，壳聚糖的伤口愈合特性可能会通过减少过多的中性粒细胞从而减轻炎症反应而得到增强。
