Lymphocyte adhesion molecule

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

Inhibition of inflammatory cytokines (Fig. 2) Humanized monoclonal anti-TNF antibodies (Infliximab (Remicade ), Adalimumab (Humira )) bind with high selectivity to human TNF-a and neutralize its activity. Thereby, infliximab decreases the effects of enhanced TNF levels during inflammatory disease such as production of proteases, chemokines, adhesion molecules, cyclooxygenase products (prostaglandins), and proinflammatory molecules such as interleukin-1 and -6. The antibodies may also recognize membrane-bound TNF-a on lymphocytes and other immune cells. These cells may subsequently become apoptotic or are eliminated via Fc-receptor-mediated phagocytosis. 

In the specialized environment of secondary lymphoid tissues such as lymph nodes or spleen, dendritic cells provide the requirements for naive T-lymphocytes to become activated and to proliferate. The professional antigen-presenting cells present peptides in MHC II, express costimulatory molecules, and release cytokines into the immunological synapse, which is formed by the antigen-presenting cell and the naive T-lymphocyte. Thus, cells of innate immunity initiate and facilitate the activation of naive lymphocytes, and it is easily conceivable that their cytokines and adhesion molecules will instruct the naive T-lymphocyte during activation and differentiation to T-effector cells. 

Key PMN, polymorphonuclear leukocytes EC, endothelial cell lymphs, lymphocytes CD, cluster of differentiation iCAM, intercellular adhesion molecule LFA-1, lymphocyte function-associated antigen-1 PECAM-1, platelet endothelial cell adhesion cell molecule-1. 

It is accepted that oxidation of LDL is a key event in endothelial injury and dysfunction. Oxidised LDL (oxLDL) may directly injure the endothelium and trigger the expression of migration and adhesion molecules. Monocytes and lymphocytes interact with oxLDL and the phagocytosis which follows leads to the formation of foam cells, which in turn are associated with the alteration of the expression pattern of growth regulatory molecules, cytokines and pro-inflammatory signals. The proposed role of oxLDL in atherogenesis, based on studies in vitro, is shown in Fig. 2.1. 

LAD Leucocyte adhesion deficiency LAK Lymphocyte-activated killer (cell) LAM, LAM-1 Leucocyte adhesion molecule, -1... 

Proinflammatory TNF-a Macrophages, monocytes, B lymphocytes, T lymphocytes, fibroblasts Induces IL-1, IL-6, IL-8, GM-CSF stimulates fibroblasts to release adhesion molecules... 

C8. Carlos, T Swartz, R Kovach, N. L., Yee, E., Rosso, M., Osbom, L. C Rosso, G., Newman, B Lobb, R., and Harlan, J., Vascular cell adhesion molecule-1 (VCAM-1) mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells. Blood 76, 965-970 (1990). 

Induction of expression of various adhesion molecules on the surface of vascular endothelial cells. These act as docking sites for neutrophils, monocytes and lymphocytes, facilitating their accumulation at local sites of inflammation. 

Sanders, M.E.. et al., Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, andLFA-1) and three other molecules(UCHLl, CDw29, Pgp-1) and have enhanced IFN-gamma production, J. Immunol, 140, 1401, 1988. 

H8. Horst, E., Meijer, C., Radaszkiewicz, T., Ossekoppele, G., Van Krieken, J., and Pals, S. T., Adhesion molecules in the prognosis of diffuse large cell lymphoma expression of a lymphocyte homing receptor (CD44), LFA-1 (CDIIa/18) and ICAM-1 (CD54). Leukaemia 4, 595-599 (1990). 

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