Subject selectins

Cell Adhesion. The membranes of leukocytes and platelets contain a variety of components that promote ceU-surface contact. Although numerous ceU-surface molecules are likely to play a role in ceU-surface adhesion, the group of selectins are of particular interest to research on this subject. Selectins are molecules that are known to promote leukocyte—platelet adhesion. However, selectin-based models have not been able to account for the fact that platelets are allowed to pass through the filter and leukocytes are not. 

In 27 postmenopausal subjects who took estradiol for 8 weeks, either alone or in combination with the progestogen norethisterone, there was an increase in plasma thromboxane beta2 concentration, possibly determined by platelet activation, which suggests an increased shortterm risk of thrombosis P-selectin expression was not affected (54). 

Inflammation is an important factor in the development of cardiovascular disease. Most clinical studies involving inflammation parameters have been relatively small. The Nurses Health Study involving 727 women was the largest study designed to determine the effects of n-3 fatty acids on biomarkers of inflammation and endothelium activation (Lopez-Garcia et al., 2004). They found an inverse association between ALA intake and plasma concentrations of C-reactive protein (a marker for inflammation), Interlukin-6, and E-selectin. Bemelmans et al. (2004) also found an inverse association between C-reactive protein and ALA intake in a randomized, double-blind placebo-controlled study involving 103 hypercholesterolemic subjects. 

In contrast to the high affinity biotin-(strept)avidin bonds, carbohydrate-L-selectin bonds with modest affinity stop white cells at vessel walls in the circulation. Numerous bonds to other surface (integrin) receptors then form between the white cell and vessel wall to sustain adhesion and enable subsequent movement into the surrounding tissue. On its initial arrest from the blood flow, the white cell can be subjected to forces of 100 pN in a time frame of milliseconds, which implies loading rates of lO -lO pN s . With this functional requirement in mind, we now examine recent tests of carbohydrate-L-selectin bonds under dynamic loading in probe tests. 

Upregulation of adhesion molecules has been documented in human stroke patients [7]. It was demonstrated that leukocytes from patients suffering an ischemic stroke or transient ischemic attack showed increased CDl la expression within 72 hours of the onset of symptoms [123]. Increased ICAM-1 expression on the surface of vessels fi om cerebral cortical infarcts was detected in four patients [124]. In some studies, soluble isoforms of adhesion molecules shed fi om the surfaces of activated cells were quantified in serum. Serum endothelial-leukocyte adhesion molecule-1 (ELAM-1, E-selectin) levels increased up to 24 hours after stroke. Similar increases were observed in serum vascular cell adhesion molecule-1 (VCAM-1) levels and these increases were sustained up to 5 days [125]. In contrast, serum ICAM-1 levels in acute ischemic stroke patients have been found to be lower than or the same as those of asymptomatic control subjects matched for age, sex, and vascular risk factors [125,126]. The reason not to detect an increase in serum levels of adhesion molecules might be due to the late enrolling of patients. Once adhesion molecules bind to leukocytes and endothelial cells, they can no longer be detected in serum [7]. 

The involvement of sialic acid in the interaction of leukocyte adhesion receptors of the selectins with their ligands has been a subject of numerous reviews. It is obvious from these studies that sialic acid is involved in this interaction because of the charge of its carboxylic group that can be substituted with sulfate [220]. More recently, selectin/mannose-binding protein chimeras have been constructed to understand the mechanism involved in the binding of sialylated Lexis oligosaccharide by this receptor [221]. 

The topic of selectins and their role as vascular adhesion molecules has been the subject of expert reviews. " ... 

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