Mechanisms responsible for enhanced inflammatory response to ischemia-reperfusion in diabetes.
The objective of the present study was to assess the role of lipid mediators and adhesion molecule expression in exacerbation of ischemia-reperfusion-induced inflammatory response in diabetes. Leukocyte-endothelial cell interactions were studied in mesenteric venules by intravital microscopy. Endothelial expression of intercellular adhesion molecule (ICAM)-1 was measured by the double-radiolabeled monoclonal antibody technique, and beta2-integrin expression was measured by flow cytometry. Ischemia-reperfusion elicited significantly larger increases in leukocyte adhesion and emigration in diabetic rats that were prevented by a platelet-activating factor (PAF)-receptor antagonist or a leukotriene synthesis inhibitor. Leukotriene B4 (LTB4) superfusion induced similar leukocyte recruitment in diabetic and control rats, whereas PAF elicited larger increases in diabetic rats. CD11a, but not CD11b, expression was higher in leukocytes from diabetic animals. Endothelial ICAM-1 in mesentery and in intestine did not differ between diabetic and control rats. These results indicate that diabetes is associated with an enhanced response to ischemia-reperfusion that depends on both PAF and leukotrienes. An increased sensitivity to PAF, along with an increased CD11a expression, may account for the exaggerated inflammatory response to ischemia-reperfusion in diabetes.
Salas
A
A
Gastroenterology Department, Hospital Clínic, Barcelona 08036, Spain.
Panés
J
J
Elizalde
J I
JI
Casadevall
M
M
Anderson
D C
DC
Granger
D N
DN
Piqué
J M
JM
D000818:Animals; D018845:CD11 Antigens / Q000276:immunology; D018821:CD18 Antigens / Q000096:biosynthesis / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000503:physiopathology*; D007249:Inflammation / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000276:immunology* / Q000503:physiopathology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled
D018845:CD11 Antigens; D018821:CD18 Antigens; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D018799:Intercellular Adhesion Molecule-1; D007975:Leukotriene B4