Effects of Heparin and Its Desulfated Derivatives on Leukocyte-Endothelial Adhesion

Abstract

The effect of heparin and partially desulfated heparin derivatives on thrombin and PAF-induced adhesion of PMNs to the endothelium was studied either by a fluorescence image analysis or by 111In-labeled PMNs. The results observed with these two techniques consistently indicated that heparin and O-des-heparin inhibited PMN adhesion in a dose-dependent manner. Moreover, N-des-Hep and N-O-des-Hep, even if less effective, also inhibited the adhesion of PMNs when used at high concentrations. The effect of heparin and heparin derivatives was not directed to endothelial cells but rather to PMNs, as shown by the absence of inhibitory effects, when heparins were preincubated with endothelium.

The effects of heparin on the adhesion of human peripheral blood mononuclear cells to human stimulated umbilical vein endothelial cells

“…The results of our study demonstrate that heparin is able to modulate the adhesion of mononuclear cells to vascular endothelial cells in vitro, in addition to its previously reported e ects on granulocyte adhesion (Bazzoni et al, 1992;Lever et al, 2000;Silvestro et al, 1994). However, we have found that depending upon the stage at which heparin is introduced to the adhesion assay, di erential e ects are observed, a phenomenon which would appear to be restricted to mononuclear cells, given that an inhibitory e ect on neutrophil adhesion is seen under all the experimental conditions Figure 6 E ect of charged molecules on HPBMNC adhesion to HUVECs.…”

“…However, if this were the case, one might expect the same e ect to occur with neutrophils when, in fact, the opposite is seen. Moreover, binding of the integrin adhesion molecule mac-1 (Diamond et al, 1995) on neutrophils has been suggested to be at least partially responsible for the inhibitory e ects of heparin on neutrophil adhesion (Salas et al, 2000;Silvestro et al, 1994). It is, however, plausible that such a`bridging' e ect may depend on the concentration of heparin available in the system and whether soluble or bound.…”

“…In addition, heparin is known to bind a number of adhesion molecules involved in leucocyte tra cking into tissues, including mac-1 (CD11b/CD18; Diamond et al, 1995) and L-selectin (Koenig et al, 1998) on in¯ammatory cells and the endothelial adhesion molecules P-selectin (Revelle et al, 1996;Skinner et al, 1991) and platelet endothelial adhesion molecule-1 (PECAM-1; Watt et al, 1993). Accordingly, heparin and related molecules have been found to inhibit leucocyte-endothelial interactions both in vitro (Bazzoni et al, 1992;Lever et al, 2000;Silvestro et al, 1994) and in vivo (Ley et al, 1991;Salas et al, 2000;Xie et al, 1997), as well as in¯ammatory cell accumulation in tissue sites such as the lung (Sasaki et al, 1993;Seeds et al, 1993), skin (Teixeira & Hellewell, 1993) and peritoneal cavity (Nelson et al, 1993). …”

Pharmacology of Heparin and Related Drugs

“…Heparin has been shown to inhibit the adhesion of leukocytes to endothelium both in vitro (Bazzoni et al, 1993;Silvestro et al, 1994;Lever et al, 2000;Smailbegovic et al, 2001) and in vivo (Ley et al, 1991;Tangelder and Arfors, 1991;Nelson et al, 1993;Xie et al, 1997;Salas et al, 2000;Johnson et al, 2004;Lever et al, 2010). Furthermore, the ultimate accumulation of cells in inflamed tissue sites, in response to both allergic (Sasaki et al, 1993;Seeds et al, 1995;Seeds and Page, 2001;Vancheri et al, 2001) and nonallergic (Nelson et al, 1993;Teixeira and Hellewell, 1993;Yanaka and Nose, 1996;Johnson et al, 2004;Lever et al, 2010) stimuli, is inhibited by heparin.…”

Adhesion inhibition “in vitro” by heparin derivatives correlates with their activity on angiogenesis in mice

“…Short Communication studied a series of de-sulphated heparin derivatives [3]. These products present relevant characteristic having almost no anticoagulant activity and being absorbed, at a significant extent, orally.…”