Binding to Glycosaminoglycans

Heparin cofactor II, when activated by binding to glycosaminoglycans (dermatan sulfate, heparins, and heparin), inhibits thrombin (24). The 43-kDa serpin, proteinase nexin 1, possesses 30% sequence homology with ATIII and can be activated by binding to heparin to inhibit several serine proteinases including thrombin (25). Proteinase nexin 2 is found within the platelet a-granule and is released when platelets are activated (26). It is able to inhibit factor XIa. 

An old hypothesis is based on the observations of Dahlen et al. (D3), who demonstrated that above a certain concentration in plasma, Lp(a) could bind to glycosaminoglycans in the arterial wall (B12). Colocalization of Lp(a) and fibrin on the arterial wall can lead to oxidative changes in the lipid moiety of Lp(a) and induce the formation of oxidatively modified cholesterol esters, which in turn can influence the interaction of Lp(a) and its receptors on macrophages. This process is promoted by the presence of calcium ions. Cushing (C14), Loscalzo (L22), and Rath (R3) reported a colocalization of undegraded Lp(a) and apo-Bl00 in the extracellular space of the arterial wall. In contrast to LDL, Lp(a) is a substrate for tissue transglutaminase and Factor XUIa and can be altered to products that readily interact with cell surface structures (B21). 

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a member of the IgG superfamily found on various cells and may bind to glycosaminoglycans. There are nine potential 7V-glycosylation sites [101] but no detailed investigations have been done. 

Figure 9 Structures of the two forms of lymphotactin, a human chemokine. Ltnl 0 activates XCR1 on leukocytes, whereas Ltn40 binds to glycosaminoglycans on cell surfaces. Reproduced with permission from R. L. Tuinstra F. C. Peterson S. Kutlesa E. S. Elgin M. A. Kron B. F. Volkman, Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 5057-5062.

Saito A, Munakata H. Analysis of plasma proteins that bind to glycosaminoglycans. Biochim Biophys Acta 2007 1770 241-624. 

Theoleyre S, Kwan Tat S, Vusio P, Blanchard F, Gallagher J, Ricard-Blum S, Fortun Y, Padrines M, Redini F, Heymann D. Characterization of osteoprotegerin binding to glycosaminoglycans by surface plasmon resonance role in the interactions with receptor activator of nuclear factor kap-paB ligand (RANKL) and RANK. Biochem Biophys Res Commun 2006 347 460-467. 

Each of these methods samples only cells and soluble inflammatory products in the airspaces. Cells in the vascular and interstitial compartments are not recoverable, and there has been debate about whether adherence characteristics of air space cells modify cellular recovery. Neither method is likely to recover proteins that precipitate in the airspaces, and neither can sample precisely inflammatory products such as chemokines that bind to glycosaminoglycans and other structures in the lungs. Nevertheless, the measurements of cell populations and inflammatory products in BAL and edema fluid provide an estimate of the amounts that are actually present in the air space compartment of the lungs. The inability to accurately sample the total concentrations of specific inflammatory products in the lungs may account for some of the variability seen in clinical studies, and some of the difficulties that have been encountered in correlating BAL and edema fluid findings with clinical variables. 

Biology of CC Chemokines and Their Receptors X. CHEMOKINE BINDING TO GLYCOSAMINOGLYCANS... 

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