Adhesion Molecules

The migration of leukocytes from the bloodstream into inflamed tissue requires a cascade of events in the microcirculation (41). The sequence of bind-

rolling cell-activation adhesion migration rolling cell-activation adhesion migration

endothelial cell endothelial ligand

VCAM-1 ICAM-1

MAdCAM-1 lCAM-2

Figure 7 The migration of leukocytes from the bloodstream to the tissue starts with rolling of the leukocytes, which is mediated by selectins. Chemoattractants or cytokines increase the expression of adhesion molecules on the endothelium or increase the avidity of the integrins on the leukocytes, leading to adhesion of leukocytes to the endothelium and finally to emigration from the bloodstream.

endothelial cell endothelial ligand

VCAM-1 ICAM-1

MAdCAM-1 lCAM-2

Figure 7 The migration of leukocytes from the bloodstream to the tissue starts with rolling of the leukocytes, which is mediated by selectins. Chemoattractants or cytokines increase the expression of adhesion molecules on the endothelium or increase the avidity of the integrins on the leukocytes, leading to adhesion of leukocytes to the endothelium and finally to emigration from the bloodstream.

ing events starts with leukocytes rolling along the endothelium (Fig. 7). This first step is mediated by selectins (42-47). Upon activation by inflammatory signals such as chemoattractants, rolling progresses to firmer adhesion, due to interaction of the integrins on leukocytes with adhesion molecules of the immunoglobulin family, such as ICAM-1 or VCAM-1, on the endothelium. Monoclonal antibodies that interfere with different steps of the cell-binding cascade have shown a beneficial effect on ischemia-reperfusion injury (48).

Enhanced expression of ICAM-1 and P-selectin has been demonstrated in the diabetic human retina and choroid (49). This increased expression of cell adhesion molecules may contribute to the retinal and choroidal microangiopathy in diabetic patients. A potential mechanism for the accelerated vasculo-pathy has been proposed recently (14). The interaction of AGEs with their endothelial receptor induced the expression of VCAM-1 in cultured human endothelial cells and in mice (14). AGE-RAGE interaction generates free radicals that activate NF-kB. NF-kB regulates in addition to other genes the expression of VCAM-1. The incubation of human umbilical vein endothelial cells with AGE increased the endothelial expression of VCAM-1. Preincubation of the cells with lipoic acid suppressed VCAM-1 expression to baseline levels (50). The AGE-induced endothelial binding of monocytes was also reduced by lipoic acid (50).

Soluble adhesion molecules are detectable only in small quantities in the serum of healthy individuals (51,52). However, increased serum levels of soluble adhesion molecules have been described in different pathologic situations, including ischemia-reperfusion injuries (53,54), insulin-dependent (IDDM) (55), and non-insulin-dependent diabetes mellitis (NIDDM) (56). In IDDM, circulating ICAM-1 and VCAM-1 but not ELAM-1 was elevated. The increased levels were found in IDDM patients with and without microangiopathy. In first-degree relatives of NIDDM, the levels of E-selectin relates to vascular risk in contrast to soluble VCAM-1, which showed no difference compared with control subjects (56). Thus, elevated levels of circulating adhesion molecules can be used as a risk marker for developing microangiopathy. The pathophysiological role of the circulating adhesion molecules is unclear. It might be that they just indicate endothelial cell stimulation by oxidative stress or that they are a reaction to protect the endothelium from further leukocyte attack. The second hypothesis might be reasonable because we could recently demonstrate that leukocyte adhesion during ischemia-reperfusion can be reduced by the application of naturally occurring soluble recombinat ICAM-1 (57).

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook


Post a comment