LEUKOCYTE-ENDOTHELIAL INTERACTIONS Adhesion Molecules in Tethering and Rolling
Victor R. Preedy in Adhesion Molecules, 2010
Chemokines and chemoattractant compounds upregulate the function of leukocyte integrins and promote their binding to counter ligands expressed on the vascular endothelium (Ley et al. 2007). Integrins are relatively unique in that their activity can be regulated independent of their expression level. Th ese interactions result in fi rm (non-rolling) adhesion and are involved in the subsequent transmigration across the endothelial layer and movement through the surrounding tissue. Integrins of the β2 family, including lymphocyte function associated antigen 1 (LFA-1, integrin αLβ2, CD11a/CD18) and macrophage-1 antigen (Mac-1, integrin αMβ2, CD11b/CD18), and the β1 family, including VLA-4 (integrin α4β1, CD49d/ CD29), have been shown to be crucial elements of the leukocyte recruitment pathway in skin and other tissues.
Endothelial and White Cell Activation in Bypass and Reperfusion Injury: Brain Injury
Richard A. Jonas, Jane W. Newburger, Joseph J. Volpe, John W. Kirklin in Brain Injury and Pediatric Cardiac Surgery, 2019
The role of endothelial and leukocyte adhesion molecules in the vascular damage and subsequent organ dysfunction related to cardiopulmonary bypass is an emerging area of interest that is based on the intense and continuing basic discoveries in the area of cellular adhesion research. Leukocyte and endothelial adhesion and subsequent activation underlie both the vascular injury resulting from extracorporeal circulation per se as well as that resulting from the ischemia and reperfusion that occur during bypass and circulatory arrest. Such injury may well underlie a substantial proportion of the brain injury resulting from pediatric cardiac surgery. Subsequent adherence to specific endothelial ligands plays a role in localization of leukocytes in specific vascular beds in poorly understood ways and also appears to result in secretory functions by the leukocyte. Deliberate, hypothermic ischemia with subsequent reperfusion is used routinely during clinical cardiopulmonary bypass in specific organ beds and, as total circulatory arrest, in the entire body including the brain.
CHAPTER
Victor R. Preedy in Adhesion Molecules, 2010
Selective recruitment of lymphocyte populations to the skin and other tissues is a crucial element of both immune surveillance and immune response to specifi c stimuli. Dysregulation of leukocyte recruitment plays a key role in the pathogenesis of various skin diseases, including infl ammatory disorders such as atopic dermatitis or psoriasis, and in the evasion of immune defenses by malignancies, such as squamous cell carcinoma and melanoma. Leukocyte homing depends on the stepwise interaction of blood cells in fl ow with the vascular wall. Each step in this cascade is necessary, but not suffi cient, to direct recruitment and retention of individual cells at a defi ned site of interest. Together they provide specifi city of site and selectivity in leukocytes recruited, as well as protection against inappropriate accumulation of eff ector leukocytes. Th erapeutic strategies targeting key molecules in the recruitment paradigm have proved eff ective and promise to provide even more options for tissue-and/or cell-selective manipulation of leukocyte homing. In this chapter, we discuss the current model of tissue-specifi c leukocyte recruitment, focusing on skin, and the role of adhesion receptors in regulating primary and memory immune responses.
Leukocyte Cell Adhesion Proteins: from Molecular Dissection to Clinical Applications
Published in Annals of Medicine, 1992
Carl G. Gahmberg, Pekka Nortamo, Rui Li, Leena Valmu
Leukocyte adhesion is needed for a number of leukocyte functions like immunoglobulin synthesis, T and NK-cell-mediated cytotoxicity, phagocytosis by granulocytes, and cellular accumulation in inflamed tissue. Several cell surface molecules involved in leukocyte-leukocyte and leukocyte-target cell interactions have recently been indentified and characterized. Both the polypeptide and carbohydrate portions are important in leukocyte interactions. It is becoming increasingly apparent that it is possible to interfere with the normal functions of the leukocyte adhesion glycoproteins, and such applications may become important in medicine.
Regulation of Leukocyte Recruitment by Local Wall Shear Rate and Leukocyte Delivery
Published in Microcirculation, 2004
MICHAEL B. KIM, INGRID H. SARELIUS
Objective: To determine the influence of wall shear rate and leukocyte delivery on leukocyte margination, rolling, and adhesion in post-capillary venules. Methods: Leukocyte–endothelial cell interactions were characterized in cremaster muscle venules of anesthetized mice with video microscopy under control conditions and after 3 h exposure to TNF-α. Hemodynamic parameters were measured with fluorescent particle tracking using confocal microscopy. Results: Leukocyte recruitment to the vessel wall and leukocyte rolling increased as a function of wall shear rate (P < 0.05) over the range observed (0–200 s−1) in intact post capillary venules. Leukocyte delivery affected recruitment and rolling flux only in activated vessels (P < 0.05). In addition, leukocyte firm adhesion was independent of both wall shear rate and leukocyte delivery, but showed an overall increase in TNF-α stimulated tissues (0.9 ± 0.2 vs. 2.7 ± 0.6 cells/50 μm). Conclusions: Leukocytes are delivered to venules in excess of the capacity of the local endothelium to support interactions. Elevated shear forces increase leukocyte recruitment to the vessel wall, which correlates to elevated rolling flux. In contrast, leukocyte firm adhesion is primarily affected by the activation state of the tissue and not by hemodynamic factors. Overall, the capacity of endothelial cells to support leukocyte interactions primarily regulates leukocyte recruitment and is not limited by leukocyte supply.
Leukocyte Agglutinins in Collagen Disease
Published in Acta Rheumatologica Scandinavica, 1957
Summary Leukocyte-iso-agglutinins were found in 18 of 40 patients with collagen diseases (rheumatoid arthritis, systemic lupus erythematosus, scleroderma, Felty's syndrome and other collagen diseases). Most frequently leukocyte agglutinins were found in systemic lupus erythematosus. A relation was found between the occurrence of leukocyte agglutinins and previous blood transfusions whereas no association between leukocyte agglutinins and pregnancies was demonstrable. Finally, leukocyte agglutinins were found in four patients who had not been subjected to iso-immunisation. Type specificity of the agglutinins could not be demonstrated. The leukocyte agglutinins were unrelated to red cell antibodies and to the L.E. factor. It is discussed whether leukocyte agglutinins may be a cause of leukopenia in collagen disease.