Department of Ophthalmology, University of Cincinnati, Cincinnati, OH 45267-0838, USA.
J Cell Sci. 2010 Sep 1;123(Pt 17):2987-95. doi: 10.1242/jcs.068221. Epub 2010 Aug 10.
An important aspect of wound healing is the recruitment of neutrophils to the site of infection or tissue injury. Lumican, an extracellular matrix component belonging to the small leucine rich proteoglycan (SLRP) family, is one of the major keratan sulfate proteoglycans (KSPGs) within the corneal stroma. Increasing evidence indicates that lumican can serve as a regulatory molecule for several cellular processes, including cell proliferation and migration. In the present study, we addressed the role of lumican in the process of extravasation of polymorphonuclear leukocytes (PMNs) during the early inflammatory phase present in the healing of the corneal epithelium following debridement. We used Lum(-/-) mice and a novel transgenic mouse, Lum(-/-),Kera-Lum, which expresses lumican only in the corneal stroma, to assess the role of lumican in PMN extravasation into injured corneas. Our results showed that PMNs did not readily invade injured corneas of Lum(-/-) mice and this defect was rescued by the expression of lumican in the corneas of Lum(-/-),Kera-Lum mice. The presence of lumican in situ facilitates PMN infiltration into the peritoneal cavity in casein-induced inflammation. Our findings are consistent with the notion that in addition to regulating the collagen fibril architecture, lumican acts to aid neutrophil recruitment and invasion following corneal damage and inflammation.
伤口愈合的一个重要方面是中性粒细胞向感染或组织损伤部位的募集。赖氨酰聚糖蛋白聚糖(lumican)是细胞外基质的一种成分,属于小富含亮氨酸的蛋白聚糖(SLRP)家族,是角膜基质中主要的硫酸角质素蛋白聚糖(KSPGs)之一。越来越多的证据表明,lumican 可以作为几种细胞过程的调节分子,包括细胞增殖和迁移。在本研究中,我们研究了赖氨酰聚糖蛋白聚糖在角膜上皮清创后愈合过程中早期炎症阶段中性粒细胞(PMN)渗出过程中的作用。我们使用 Lum(-/-) 小鼠和一种新型的转基因小鼠 Lum(-/-),Kera-Lum 来评估 lumican 在 PMN 渗出到受伤的角膜中的作用,该转基因小鼠仅在角膜基质中表达 lumican。我们的结果表明,PMN 不易浸润 Lum(-/-) 小鼠受伤的角膜,而在 Lum(-/-),Kera-Lum 小鼠角膜中表达 lumican 则可以挽救这种缺陷。原位存在的 lumican 有利于在酪蛋白诱导的炎症中 PMN 渗透到腹腔中。我们的发现与以下观点一致,即除了调节胶原纤维结构外,lumican 还可以促进角膜损伤和炎症后中性粒细胞的募集和浸润。