Leukocyte activation

With either type of dialysis, studies suggest that recovery of renal function is decreased in ARF patients who undergo dialysis compared with those not requiring dialysis. Decreased recovery of renal function may be due to hemodialysis-induced hypotension causing additional ischemic injury to the kidney. Also, exposure of a patient s blood to bioincompatible dialysis membranes (cuprophane or cellulose acetate) results in complement and leukocyte activation which can lead to neutrophil infiltration into the kidney and release of vasoconstrictive substances that can prolong renal dysfunction.26 Synthetic membranes composed of substances such as polysulfone, polyacrylonitrile, and polymethylmethacrylate are considered to be more biocompatible and would be less likely to activate complement. Synthetic membranes are generally more expensive than cellulose-based membranes. Several recent meta-analyses found no difference in mortality between biocompatible and bioincompatible membranes. Whether biocompatible membranes lead to better patient outcomes continues to be debated. 

The endothelium has many diverse functions that enable it to participate in in-flammatoiy reactions (H27). These include modulation of vascular tone, and hence control of local blood flow changes in structure that allow leakage of fluids and plasma proteins into extravascular tissues local accumulation and subsequent extravasation into tissues of leukocytes and synthesis of surface molecules and soluble factors involved in leukocyte activation (B43). The endothelial cells themselves can modulate vascular tone by the release of vasoactive substances such as prostacyclin, nitric oxide (NO), ET. Endothelium-derived vasoactive substances... 

Ml9. Meinhold, H., Gramm, H. J Meissner, W., Zimmermann, J., Schwander, J., Dennhardt, R., and Voigt, K., Elevated serum diiodotyrosine (DIT) in severe infections and sepsis DIT, a possible new marker of leukocyte activity. J. Clin, Endocrinol. Metab. 72,945-953 (1991). 

Nemmar, A. et al. (2007) Enhanced peripheral fhrombogenidty after lung inflammation is mediated by platelet-leukocyte activation role of P-selectin. Journal of Thrombosis and Haemostasis,... 

Mickelson JK, Lakkis NM, VillarrealLevy G, Hughes BJ, Smith CW. Leukocyte activation with platelet adhesion after coronary angioplasty a mechanism for recurrent disease. J Am Coll Cardiol 1996 28 345-353. 

Kaever, V., and Resch, K. (1990). Role of cyclic nucleotides in lymphocyte activation. In Current Topics in Membranes and Transport Mechanisms of Leukocyte Activation (S. Grinstein and O. D. Rotstein, ed.), Vol. 35, pp. 375-398. Academic Press, San Diego. 

Adalimumab, etanercept, and infliximab are antibodies that bind TNF- , a proinflammatory cytokine. Blocking TNF-afrom binding to TNF receptors on inflammatory cell surfaces results in suppression of downstream inflammatory cytokines such as IL-1 and IL-6 and adhesion molecules involved in leukocyte activation and migration. An increased risk of lymphoma is common to each of these agents. 

Santos-Silva, A., Rebelo, M. I., Castro, E. M. B., Belo, L., Guerra, A., Rego, C., and Quintanilha, A., Leukocyte activation, erythrocyte damage, lipid profile and oxidative stress imposed by high competition physical exercise in adolescents. Clin. Chim. Acta 306, 119-126 (2001). 

Evangelista V Manarini S, Dell ElbaG, etal. Clopidogrel inhibits platelet-leukocyte adhesion and platelet-dependent leukocyte activation. Thromb Haemost 2005 94 568-577. 

Kahlke, B., Brasch, J., Christophers, E., and Schroder, J. M. (1996) Dermatophytes contain a novel lipidlike leukocyte activator. J. Invest. Dermatol. 107, 108-112. 

U9. Ushijima, Y., Totsune, H., Nishida, A., and Nakano, M., Chemiluminescence from human polymorphonuclear leukocytes activated with opsonized zymosan. Free Radicals Biol. Med. 22, 401 109 (1997). 

Fig. 2.8. Factors controlling the production of free radicals in cells and tissues (Rice-Gvans, 1990a). Free radicals may be generated in cells and tissues through increased radical input mediated by the disruption of internal processes or by external influences, or as a consequence of decreased protective capacity. Increased radical input may arise through excessive leukocyte activation, disrupted mitochondrial electron transport or altered arachidonic acid metabolism. Delocalization or redistribution of transition metal ion complexes may also induce oxidative stress, for example, microbleeding in the brain, in the eye, in the rheumatoid joint. In addition, reduced activities or levels of protectant enzymes, destruction or suppressed production of nucleotide coenzymes, reduced levels of antioxidants, abnormal glutathione metabolism, or leakage of antioxidants through damaged membranes, can all contribute to oxidative stress.

Bokoch, G. M. (1995). Chemoattractant signaling and leukocyte activation. Blood 86, 1649-1660. 

Poluektova L, Morarr T, Zelivyanskaya M, Swindells S, Gendelmari HE, Persidsky Y (2001) Hie regulation of alpha chemokhies during HIV-1 infection and leukocyte activation Relevance for HIV-1-associated dementia. J Neui oimmunol 120 112—128. 

A. M. Elneihoum, P. Falke. L. Axelsson, E. Lundberg. F. Lindgarde, and K. Ohlsson, Leukocyte Activation Detected by Increased Plasma Levels of Inflammatory Mediators in Patients with Ischemic Cerebrovascular Diseases, Stroke. 27 (1996) 1734-1738. 

Leukocyte-endothelial adhesion, vascular obstruction, leukocyte activation, and inflammation... 

Figure 4.1. Schematic representation of leukocyte transmigration induced by chemokines. The first step involves rolling attributed to interaction between the leukocyte and the endothelial cells. This process is mediated by selectins and selectin ligands expressed on the surface of both cell types. In the next step a chemokine interacts with its receptor, inducing leukocyte activation and conformational changes in the adhesion molecules (integrins) and resulting in firm adhesion to the endothelial surface. It is believed that the chemokine is immobilized on the endothelial surface by interactions with glycosaminoglycans. The leukocytes then transmigrate into the tissues.

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