Adhesion Molecule Expression in Postischemic Microvascular Dysfunction: Activity of a Micronized Purified Flavonoid FractionKorthuis R.J. · Gute D.C.
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, School of Medicine in Shreveport, Shreveport, La., USA
Ischemia and reperfusion (I/R) induces neutrophil infiltration in skeletal muscle that is localized to the ischemic region. To transmigrate at ischemic regions, granulocytes must first arrest in the postcapillary venular segment of the microcirculation. Initially, leukocytes roll along the endothelium of these venules, a weak adhesive interaction that is mediated by the selectins (L-, E-, and P-selectin). Leukocyte rolling functions to slow the neutrophil during its transit through the microcirculation, thereby allowing it to monitor its local environment for the presence of activating factors arising from the ischemic tissues. When activated, the rolling granulocyte is rendered capable of forming the stronger adhesive interactions that allow the cell to become arrested in postcapillary venules in the ischemic region. These adhesive interactions are mediated by a leukocyte glycoprotein complex designated CD11/CD18 and intercellular adhesion molecule-1 (ICAM-1) expressed on endothelial cells. The stationary neutrophil uses the gradient in concentration of soluble chemoattractants liberated from ischemic tissues as a directional cue to move from the vascular to extravascular compartment, being guided in its transit across the endothelium by interactions with platelet endothelial cell adhesion molecule-1 (PECAM-1), an adhesive molecule localized to the interendothelial cleft. This paper reviews current understanding of the mechanisms underlying the establishment of leukocyte/endothelial cell interactions in postischemic skeletal muscle in terms of specific adhesion molecules that participate in neutrophil sequestration after I/R. Discovery of the molecular determinants of neutrophil/endothelial cell adhesion has uncovered potential mechanisms whereby agents exhibiting anti-adhesive properties may act. The micronized purified flavonoid fraction (450 mg diosmin, 50 mg hesperidin) prevents I/R-induced leukocyte adhesion in skeletal muscle. This anti-adhesive effect appears to be mediated at least in part by inhibition of induced expression of ICAM-1.
Dr. Ronald J. Korthuis, PhD
Department of Molecular and Cellular Physiology
LSU Medical Center, 1501 Kings Highway
Shreveport, LA 71130-3932 (USA)
Tel. +1 318/675 6028, Fax +1 318/675 4217, E-Mail email@example.com
This work was supported by grants from the National Institutes of Health (HL-54797 and DK-43785) and Servier.Daflon 500, also known as Detralex, Capiven, Arvenum 500, Ardium, Alvenor, Variton and Venitol.
Number of Print Pages : 9
Number of Figures : 3, Number of Tables : 0, Number of References : 31
Journal of Vascular Research
Founded 1964 as Angiologica by M. Comèl and L. Laszt (1964–1973) continued as Blood Vessels by J.A. Bevan (1974–1991)
Vol. 36, No. Suppl. 1, Year 1999 (Cover Date: Released August 1999)
Journal Editor: M.J. Mulvany, Aarhus
ISSN: 1018–1172 (print), 1423–0135 (Online)
For additional information: http://www.karger.com/journals/jvr