Endothelium interactions

Not all of the newly-synthesised PAF is released by neutrophils it is thought that release of PAF only occurs after a critical intracellular concentration has been reached even then, some PAF remains cell associated and does not act as a true extracellular effector molecule. The cell-associated PAF may thus play a role in cell-cell communication (e.g. neutrophil-neutrophil or neutrophil-endothelium interactions). Intra- and extracellular Ca2+ levels regulate both the biosynthesis and release of PAF. Increases in intracellular Ca2+ may allow PAF synthesis (but not release), whereas extracellular Ca2+ increases both synthesis and release in a dose-dependent manner. 

Sethi, S., Eastman, A.Y., and Eaton, J.W., 1996, Inhibition of phagocyte-endothelium interaction by oxidized fatty acids A natural anti-inflammatory mechanism J. Lab. Clin. Invest. 128 27-38. 

Pancreatic effect. Cigarette smoke, administered to anesthetized rats alone or in combination with iv ethanol infusion, reduced pancreatic blood flow temporarily and increased leukocyte-endothelium interaction (roller p < 0.001, sticker p < 0.01 vs baseline). Cigarette smoke potentiated the impairment of pancreatic capillary perfusion caused by ethanol, and both the number of rolling leukocytes and myeloperoxidase activity levels were increased compared with ethanol or nicotine administration alone h Tobacco-specific nitrosamines, administered to rats, induced pancreatic acinar cell and ductal cell neoplasms. One of the tumors had a mixed ductal-squamous-islet cell components . 

Elices, M. J., Osborn, L., Takada, Y., Crouse, C., Luhowskyj, S., Hemler, M. E., and Lobb, R. R. (1990). VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell 60,577-584. 

Unal C, Sen C, Iscen D, Dalcik H. In vivo observation of leukocyte-endothelium interaction in ischemia reperfusion injury with the dorsal window chamber and the effects of pentoxifylline on reperfusion injury. Journal of Surgical Research 2007, 138, 259-266. 

There are multicellular interactions that are important in inflammatory processes and in vascular remodeling. Activated platelets induce endothelial cells to secrete chemokines and to express adhesion molecules, indicating that platelets could initiate an inflammatory (Table I) response of the vessel wall. Activated platelets promote leukocyte binding to inflamed or atherosclerotic lesions (27,28). Cell adhesion molecules (CAMs) are responsible for leukocyte-endothelium interactions. It plays a crucial role in inflammation and atherogenesis. Vascular CAM-1 (VCAM-I)and intracellular CAM-1 (ICAM-I) promote monocyte recruitment to sites of injury and constitute a critical step in inflammation and in atherosclerotic plaque development. TSP-1, a matricellular protein released in abundance from activated platelets and accumulated in sites of vascular injury, induces the expression of VCAM-1 and ICAM-1 on endothelium and significantly increases the monocyte attachment (29). 

Gauthier, T.W., Scalia, R., Murohara, T., Guo, J.P, and Lefer, A.M., Nitric oxide protects against leukocyte-endothelium interactions in the early stages of hypercholesterolemia, Artenosc/eK Thromb. Vase. Biol, 15, 1652, 1995. 

Ware JA, Heistad DD. Platelet-endothelium interactions. NEngl JMed 328 628-635,1993. 

D. Pruefer, R. Scalia and A. M. Lefer, Homocysteine Provokes Leukocyte-Endothelium Interaction by Downregulation of Nitric Oxide, General Pharmacology 33 (1999) 487-498. 

Flickey MJ, Sharkey KA, Sihota EG, Reinhardt PFI, MacMicking JD, Nathan C, Kubes P Inducible nitric oxide synthase-deficient mice have enhanced leukocyte-endothelium interactions in endotoxemia. FASEB J. 11 955-964,1997... 

Figure 15. Dose dependently c-GMP inhibits PDE or activates PKG, thereby mediating its effects on the vasculature, platelets and myocytes. The cardiac interstitial NO concentration during early ischemia and early reperfusion is increased. The increase in NO concentration is derived from activated NO synthase (NOS) isoforms (species specific) and from NOS independent pathways. Cardiac c-GMP concentration during ischemia is somewhat increased while upon reperfusion is decreased. NO seems to mediate protective as well as deleterious effects which are critically dependent on the specific experimental conditions. NO at lower concentrations preserves blood flow and attenuates platelet aggregation and neutrophil-endothelium interaction following ischemia and reperfusion. In small amounts might also be beneficial by nitration of the cardioprotective PKCe. Furthermore, NO increases cardiomyocyte function. Figure 16. At higher concentrations, NO depresses cardiomyocyte function, mediates inflammatory processes following ischemia and reperfusion, impairs mitochondrial respiration...

Elamann, A., Jablonski-Westrich, D., Duijvestijn, A., Butcher, E. C., Baisch, H., Elarder, R., and Thiele, H.-G., Evidence for an accessory role of LFA-1 in lymphocyte-high endothelium interaction during homing, J. Immunol., 140, 693, 1988. 

N. Gupta, and R. R. Weichselbaum. 2003. Tumour-endothelium interactions in co-cul-ture coordinated changes of gene expression profiles and phenotypic properties of endothelial cells. J Cell Sci 116 1013. 

Radomski, M. W., Palmer, R. M. J., and Moncada, S. (1987b). The anti-aggregating properties of vascular endothelium Interactions between prostacyclin and nitric oxide. Br. J. Pharmacol. 92, 639-646. 

Lefer, A. M., Siegried, M. R., and Ma, X.-L. (1993). Protection of ischemia-reperfusion injury by sydnonimine NO donors via inhibition of neutrophil-endothelium interaction. J. Cardiovasc. Pharmacol. 22, S27-S33. 

Problems of leukocyte distribution in the microcirculation and their interaction with the microvascular endothelium have attracted considerable attention in recent years [17]. Leukocyte rolling along the walls of venules, but not arterioles, has been demonstrated. This effect results from differences in the microvascular endothelium, mainly attributed to the differential expression of adhesion molecules on the endothelial surface [24]. Platelet distribution in the lumen is important because of platelets role in blood coagulation. Detailed studies of platelet distribution in arterioles and venules show that the cross-sectional distribution of these disk-shaped blood elements is dependent on the blood flow rate and vessel hematocrit [25] molecular details of platelet-endothelium interactions are available [26]. Considerable progress has been made in computational modeling of leukocytes in microvessels and their interaction with red blood cells [27-29]. 

ICAM-1 and lymphocyte function-associated protein (LFA)-l pathway are involved in monocyte-endothelium interaction during a cholesterol-rich diet. In rats on high-cholesterol diet, ICAM-1 expression was increased on aortic EC, which was associated with increased monocyte adherence (more than 85% of adherent macrophages exhibited LFA-1 antigen and injecting the animals with ICAM-1 monoclonal antibody and LFA-1 monoclonal antibody reduced mostly LFA-1 positive macrophages) (167). In clinically healthy middle-aged men, levels of soluble ICAM-1 (sICAM-1), but not sVCAM-1 or E-selectin, were associated with subclinical atherosclerosis and inflammatory variables (168). 

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