Erythrocytes adhesion

These are indeed confusing results. However, later research provided data for a different interpretation of the above results, i.e., hesperidin did not act on the disease process but altered the ESR by direct action on blood cells (15,16,17,18). In 1966 Robbins (15) reported that hesperidin, naringin and rutin reduced the intravascular erythrocyte adhesion accompanying Vitamin C deficiency in the guinea pig. The above findings... 

Bioflavonoids have been discovered to exert an antiadhesive action on blood cells. Erythrocyte adhesion is a general accompaniment of disease and trauma and has rheological implications. Hesperidin or other of the less active fiavonoids administered to a series of patients or added to blood in vitro may show three kinds of activity, inhibit blood cell adhesion in some, no effect in others or accelerate adhesion in still others, i.e., a trimodal action. This characteristic feature of flavonoid action undoubtedly has been interpreted as an inconsistent effect. However, all fiavonoids do not show a trimodal action. Also, there is considerable evidence linking rheological effects of bioflavonoids to their effects on capillary defects and beneficial effects in disease. Thus, the trimodal effects may explain the apparent inconsistent action against the above phenomena. 

Parise LV, Telen MJ. Erythrocyte adhesion in sickle cell disease. Cur Hematol Rep 2003 2 102-108. 

Eda, S., Lawler, J., and Sherman, I. W. (1999). Plasmodium falciparum-infected erythrocyte adhesion to the type 3 repeat domain of thrombospondin-1 is mediated by a modified band 3 protein. Mol. Biochem. Parasitol. 100,195-205. 

Stamenkovic, I., and Seed, B., 1990, The B-cell antigen CD22 mediates monocyte and erythrocyte adhesion. Nature 345 74-77. 

Sickle erythrocytes have increased surface expression of CD36. Microvascular endothelial cells do express CD36. Adhesion between these CD36 molecules of the two cells types can be mediated via the bridging ligand thrombospondin". Indeed plasma thrombospondin levels are increased in SCA patients with pain crisis [15]. 

Although HU may mediate some of its clinical benefits through its positive effect on HbF expression, these data also suggest that it may, by a yet-to-be defined mechanism of action, modulate the clinical severity of SCA. One possible pathway is that among the two incriminated interacting cell partners (sickle erythrocyte and endothelial cell) involved in vaso-adhesion and occlusion, HU may also affect the phenotype status of endothelial cells so that its adhesogenic (structural) and/or vasoregulatory (functional) properties are modified in a favorable manner. 

Although ICAM-1 seems not to be involved in the sickle cell adhesion to vascular endothelium, it may exacerbate vasoocclusion by promoting leukocyte adhesion. In this context, it is remarkable to note that in HU-treated SCA patients, the strongest correlation was found between total white cell count and severity of crisis rather than with erythrocyte-related parameters [28]. The current consensus is that leukocyte endothelium adhesion may initiate vasoocclusion followed by RBC sequestration and entrapment in the microvascular lumen with ensuing painful crisis. Thus overexpression of ICAM-1 is expected to promote VOC. The data... 

Elevated ET-1 in SCA patients, even in the steady state, may play an important role in the dehydration of sickle erythrocytes and the resulting enhanced intra-erythrocytic HbS polymerization. Indeed, it has been shown that ET-1 activates Ca2+- gated K+ channels in mouse erythrocytes [34]. ET-1, as a pro-inflammatory agonist, has been shown to induce the production of inflammatory cytokines by monocytes. One of the cytokines, namely TNFa enhances the adherence of sickle erythrocytes to vascular endothelium [35]. In addition, endothehns upregulate the expression of endothelial adhesion molecules such as ICAM-l, VCAM-1 and E-se-lectin, which participate in the recruitment of white cells to the site of inflammation. The overall conclusions that can be drawn from these data is that ET-1 plays a critical role in the vasospasm and inflammation that result in VOC. The major effect of HU in ameliorating the clinical symptoms of SCA likely results from its ability to inhibit the chronically activated ET-1 expression in SCA patients. 

Hebbel R. Adhesive interactions of sickle erythrocytes with endothelium. J Clin Invest 1997 100 S83-86. 

Wick T, Kaye N, Jensen W. Unusually large von Willebrand factor multimers increase adhesion of sickle erythrocytes to human endothelial cells under controlled flow. N Engl J Med 1982 337 1584-1590. 

B. Konig, T. Fricke, A. Wa/imann, U. Krallmann-Wenzel, and T. K. Lindhorst, y-Mannosvl clusters scaffolded on azamacrocycles Synthesis and inhibitory properties in the adhesion of type 1 fimbriated Escherichia coli to guinea pig erythrocytes, Tetrahedron Lett., 39 (1998) 2307-2310. 

T. K. Lindhorst, C. Kieburg, and U. Krallmann-Wenzel, Inhibition of the type 1 fimbriae-mediated adhesion of Escherichia coli to erythrocytes by multiantenn-ary x-mannosyl clusters the effect of multivalency, Glycoconjug. /., 15 (1998) 605-613. 

Gowda, A.S.P., Madhunapantula, S.V., Achur, R.N., Valiyaveettil, M., Bhavanandan, V.P., and Gowda, D. C. (2007) Structural basis for the adherence of plasmodium falciparum-infected erythrocytes to chon-droitin 4-sulfate and design of novel photoactivable reagents for the identification of parasite adhesive proteins./. Biol. Chem. 282, 916-928. 

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