Modulation of Leukocyte Behavior by an Inflamed Extracellular Matrix

Inflammation is a response of the immune system to foreign insult or physical damage. Various cellular and humoral components of the immune system are recruited from the vascular system and are translocated through endothelium, and into extracellular matrix (ECM) compartments of inflamed tissues. This translocation is orchestrated by various types of accessory signals, in the form of soluble or complexed molecules, which evoke remarkable transitions in leukocyte activities. Recruited inflammatory cells give rise to mechanisms of migration, including the secretion of enzymes and other pro-inflammatory mediators and the alteration of their adhesive contacts with the ECM. Hence, migrating cells secrete enzymes, chemokines, and cytokines which interact with the ECM, and thereby, provide the cells with intrinsic signals for coordinating their responses. Resultant products of enzymatic modifications to the ECM microenvironment, such as cytokine- and ECM-derived molecules, may be also part of a cell-signaling mechanism that provides leukocytes with information about the nature of their inflammatory activity; such a mechanism may give the immune system data that can be cognitively interpreted for consequential activities. This article reviews the findings that support this notion and describe the dynamic interactions between participants of the inflammatory processes

Chondroitin sulfatederived disaccharide protects retinal cells from elevated intraocular pressure in aged and immunocompromised rats. Invest Ophthalmol Vis Sci.

PURPOSE. A disaccharide (DS) derived from the naturally occurring compound chondroitin sulfate proteoglycan (CSPG) was recently shown to have neuroprotective activity. The authors examined the ability of this compound (CSPG-DS) to protect retinal ganglion cells (RGCs) from death caused by elevated intraocular pressure (IOP). METHODS. With the use of chronic and acute models of elevated IOP, the authors examined the effects of CSPG-DS on RGC survival in adult (ϳ2 months old), aged (10 -12 months old), and immunocompromised Lewis rats. Systemic, topical, and oral routes of administration were examined. RESULTS. CSPG-DS protected RGCs from IOP-induced death. Treatment was effective in all three examined rat populations (normal adult, aged, and immunocompromised rats) and with all routes of administration, possibly in part through its control of microglial activity. CONCLUSIONS. Results point to the therapeutic potential of CSPG-DS for glaucoma, particularly in elderly populations for whom disease prevalence is high. (Invest Ophthalmol Vis Sci