E-selectin and its ligands are essential for extravasation of leukocytes in inflammation. Here, we report that basigin (Bsg)/CD147 is a ligand for E-selectin that promotes renal inflammation in ischemia/ reperfusion. The selectins and their ligands are essential for leukocyte tethering/rolling on endothelial cells and the initiation of inflammatory response. The selectins are C-type lectins and consist of three members, i.e., P-, L-, and E-selectin. 1,2 P-selectin is expressed upon inflammatory stimulation in platelets and endothelial cells. L-selectin is constitutively expressed on the tip of leukocyte microvilli and implicated in lymphocyte homing to lymph nodes. 3 E-selectin is specifically induced in the endothelium upon inflammatory stimulation. Thus, E-and P-selectin closely collaborate with one another and play a major role in leukocyte recruitment to inflammatory sites. 4 -6 Among the several glycoproteins reported to bind to E-selectin, three have been identified as representative physiologic E-selectin ligands on neutrophils. There are P-selectin glycoprotein ligand-1 (PSGL-1), E-selectin ligand-1, and CD44, and all three play distinct roles during tethering and slow rolling of neutrophils on the endothelium. 7 A minimal recognition motif for all selectins is sialylated and fucosylated glycan determinants, such as sialyl Lewis X, that decorate the terminal extensions of carbohydrates of these molecules. 8,9 However, because of the poor immunogenicity of highly gly-
Carbohydrate structures on PRBC are different from those on PAEC. Healthy human sera contain anti-nonGal IgG antibodies to NeuGc expressed on PRBC, but not on PAEC. We speculate that anti-nonGal IgG antibodies to PRBC can recognize both NeuGc and protein, and this may be the reason why such antibodies have not been detected by ELISA. A definite conclusion about the immunogenicity of NeuGc has not been obtained. More sera from patients (not from non-human primates) sensitized with porcine cells or organs need to be studied.
In addition to effective suppression of antibody-induced complement activation, hTM expression in PAEC may be essential for regulating procoagulant activity in xenotransplantation.
Complement inhibition by upregulation of CD55 and CD59 through ERK1/2 inactivation might play a substantial role in accommodation after ABO-incompatible transplantation, which could also explain the intriguing finding of C4d deposition in the graft without rejection.
The effects of melatonin on blood pressure and heart rate were studied in 23-week-old male spontaneously hypertensive rats. Melatonin infused i.p. at a dose of 6 mg/rat per day for 5 days using an osmotic minipump produced a significant reduction of blood pressure and a slight but significant decrease of heart rate in the conscious and unrestrained state. These cardiovascular effects of melatonin developed gradually. Plasma renin concentration tended to decrease after melatonin treatment. These results demonstrate that melatonin has an antihypertensive action. The mechanism of the antihypertensive action of melatonin requires further study.
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