Adhesiveness lymphocytes

The largest numbers of integrins are members of the (31 integrins, also known as the very late antigen (VLA) subfamily because of its late appearance after activation. There are at least seven receptors characterized from this subfamily, each with different ligand specificity. Among the most studied include the 04(31 and a5 31 receptors. The leukocyte integrin a4 31 is a cell adhesion receptor that is predominantly expressed on lymphocytes, monocytes and eosinophils. 

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. 

The leukocyte integrin a 4(3 1 (also known as VLA-4 and CD49d/CD29) is a cell adhesion receptor, which is predominantly expressed on lymphocytes, monocytes and eosinophils. VLA-4 is generally selective for the CS1 domain within fibronectin, with an essential requirement for LDV sequence for binding. VLA-4 also binds to VCAM-1 as a counter receptor. 

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. 

At cellular level each stage of atheroma development is accompanied by the expression of specific glycoproteins by endothelial cells which mediate the adhesion of monocytes and T-lymphocytes. Their recruitment and migration is triggered by various cytokines released by leukocytes and possibly by smooth muscle cells. Atheroma development continues with the activation of macrophages, which accumulate lipids and become, together with lymphocytes, so-called fatty streaks. The continuous influx, differentiation and proliferation finally leads to more advanced lesion and to the formation of the fibrous plaque. ... 

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... 

Campbell JJ, Bowman EP, Murphy K, et al. 6-C-kine (SLC), a lymphocyte adhesion-triggering chemokine expressed by high endothelium, is an agonist for the MIP-3beta receptor CCR7. J Cell Biol 1998 141 1053-1059. 

Gunn MD, Tangemann K, Tam C, Cyster JG, Rosen SD, Williams LT. A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes. Proc Natl Acad Sci U S A 1998 95(l) 258-263. 

Fig. 4. The role of RANTES in recruiting monocytes and T lymphocytes to injured endothelium involves the binding of platelets to activated endothelium in a P-selectin-dependent manner with subsequent secretion of RANTES by bound platelets. RANTES can then attract CCR5-expressing monocytes and T cells to the damaged endothelium as well as causing monocyte firm adhesion to occur via binding to platelet-derived RANTES deposited on the endothelial cell layer.

---