Leukocyte adherence to endothelial cells is an early and rate-limiting event in the overall pathogenesis of ischemia-reperfusion induced injury to the intestinal microvasculature. The propensity for leukocytes to adhere to microvascular endothelium and subsequently emigrate from the blood stream is determined by the balance between adhesive forces that are generated by membrane glycoproteins on the surface of both leukocytes (CD11/CD18) and endothelial cells (ICAM-1), and the hydrodynamic dispersal forces (e.g., erythrocyte velocity) that tend to sweep leukocytes away from the endothelial surface. The overall objective of the work outlined in this proposal is to determine how variations in shear forces, over a range that is predicted to occur during ischemia and reperfusion, influence leukocyte-endothelial cell adhesive interactions in cat mesenteric venules. The relationships among leukocyte rolling velocity, adherence and venular hemodynamics (blood flow, erythrocyte velocity, wall shear rate) will be defined in normal venules and in venules exposed to a proinflammatory stimulus (PAF or LTB4). The latter studies will allow us to determine how an increase in leukocyte adhesiveness, as occurs during ischemia- reperfusion, alters the influence of shear forces on leukocyte-endothelial cell interactions. Studies are also proposed to define the relative roles of the leukocyte and endothelial cell adhesive glycoproteins in shear rate- dependent leukocyte adherence and rolling. Immunoneutralization of CD11/CD18 and ICAM-1 will be achieved using specific monoclonal antibodies. The role of neutrophil derived oxidants (superoxide and hydrogen peroxide) will also be assessed using the antioxidant enzymes, superoxide dismutase and catalase. Another major objective of this project is to determine whether venular wall shear rate influences the ability of a leukocyte to emigrate from the vasculature in response to specific proinflammatory stimuli. The results derived from all of the studies outlined in this application should extend current knowledge regarding the leukocyte- endothelial cell adhesive interactions that occur during ischemia- reperfusion and how these interactions ultimately contribute to the microvascular dysfunction that is observed following reperfusion of ischemic tissues.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Louisiana State University Hsc Shreveport
Department
Type
DUNS #
City
Shreveport
State
LA
Country
United States
Zip Code
71103
Ma, Yuxiang; Okazaki, Yasumasa; Glass, Jonathan (2018) A fluorescent metal-sensor study provides evidence for iron transport by transcytosis in the intestinal epithelial cells. J Clin Biochem Nutr 62:49-55
Hozumi, Hideaki; Russell, Janice; Vital, Shantel et al. (2016) IL-6 Mediates the Intestinal Microvascular Thrombosis Associated with Experimental Colitis. Inflamm Bowel Dis 22:560-8
Souza, Daniele G; Senchenkova, Elena Y; Russell, Janice et al. (2015) MyD88 mediates the protective effects of probiotics against the arteriolar thrombosis and leukocyte recruitment associated with experimental colitis. Inflamm Bowel Dis 21:888-900
Yan, Serena L S; Russell, Janice; Granger, D Neil (2014) Platelet activation and platelet-leukocyte aggregation elicited in experimental colitis are mediated by interleukin-6. Inflamm Bowel Dis 20:353-62
Watts, Megan N; Eshaq, Randa S; Carter, Patsy R et al. (2013) Decreased retinal blood flow in experimental colitis; improvement by eye drop administration of losartan. Exp Eye Res 115:22-6
Watts, Megan N; Leskova, Wendy; Carter, Patsy R et al. (2013) Ocular dysfunction in a mouse model of chronic gut inflammation. Inflamm Bowel Dis 19:2091-7
Carter, Patsy R; Watts, Megan N; Kosloski-Davidson, Melissa et al. (2013) Iron status, anemia, and plasma erythropoietin levels in acute and chronic mouse models of colitis. Inflamm Bowel Dis 19:1260-5
Cromer, Walter E; Ganta, Chaitanya V; Patel, Mihir et al. (2013) VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: protective effects of a VEGF164b therapy. J Transl Med 11:207
Senchenkova, Elena Y; Komoto, Shunsuke; Russell, Janice et al. (2013) Interleukin-6 mediates the platelet abnormalities and thrombogenesis associated with experimental colitis. Am J Pathol 183:173-81
Yan, Serena L S; Russell, Janice; Harris, Norman R et al. (2013) Platelet abnormalities during colonic inflammation. Inflamm Bowel Dis 19:1245-53

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