Movement Of Immune Cells Research Articles

Adhesion molecules in cutaneous immunity.

Skin serves a vital role, providing protection from the broad array of pathogens present in our environment. In addition to the passive barrier functions of the skin, mammals have evolved a robust and versatile surveillance and rapid response system for recognition and elimination of invading organisms. This immune surveillance network directs the movement of immune cells, regulating homeostatic populations of immune cells in the skin, as well as recruitment to sites of inflammation. In this review, we discuss current understanding of the regulation and function of adhesion molecules in cutaneous immune surveillance and their relevance to the immunopathology of inflammatory skin disease.

Chemokines in Gastrointestinal Disorders

The intestine is constantly challenged by food antigens and pathogens and is therefore in need of a good working innate and adaptive immune response. Chemokines are important modulators as they assure the directed movement of immune cells within the body. In addition, chemokines play an important role in hematopoiesis, angiogenesis and tumor metastasis. This review focuses on chemokines and gastrointestinal disorders, more particularly on inflammatory bowel diseases and gastrointestinal tumors. In a first part, the current knowledge on chemokine expression in inflammatory bowel diseases is summarized. Idiopathic inflammatory bowel diseases are characterized by an uncontrolled immune response. The resulting chronic inflammation of the intestine involves massive infiltration of immune cells, causing intestinal damage by the release of cytokines and proteolytic enzymes. Chemokines are believed to be key mediators in this process of aberrant leukocyte recruitment. Chemokine expression in inflammatory bowel disease strongly correlates with the grade of disease activity. The potential therapeutic use of chemokines in gastrointestinal tumors by the use of gene therapy is also reviewed. Chemokines have therapeutic potential in anti-tumor therapy by their angiostatic effect. On the other hand, chemokines can augment the cell-mediated adaptive immune response and thereby exert anti-tumor activity. However, chemokines can passively favor escape of tumor cells by stimulating the release of tissue degrading matrix metalloproteinases and can actively promote metastasis of chemokine receptor-expressing tumor cells.

The role of chemokines in rheumatoid arthritis and osteoarthritis

The directed movement of immune cells is highly dependent on the chemokine network. Chemokines are key molecules early in the embryogenesis of lymph nodes and throughout adult life, where they regulate immune responses against pathogens. Although immune cells are best known for expressing chemokine receptors, through which they can respond to matching chemokines, endothelial cells also express chemokine receptors. The directed movement of endothelial cells facilitates angiogenesis. In chronic inflammatory conditions, such as rheumatoid arthritis (RA), chemokines are abundantly present at the site of inflammation and form a group of potential therapeutic targets. Some agents that block chemokine–chemokine receptor interaction are already under clinical investigation. The expression of chemokine receptors has also been found in cell types other than immune cells and endothelial cells. Chondrocytes, for instance, express several chemokine receptors. Elucidating their function may provide new insights into joint degradation in RA as well as in other conditions, including osteoarthritis (OA).

Human vascular adhesion protein-1 (VAP-1) plays a critical role in lymphocyte-endothelial cell adhesion cascade under shear.

Lymphocyte binding to vascular endothelium is a prerequisite for the movement of immune cells from the blood into lymphoid tissues and into sites of inflammation. Human vascular adhesion protein-1 (VAP-1) is an endothelial glycoprotein involved in this interaction. It also displays an enzymatic (monoamine oxidase) activity. Here we examined how recombinant human VAP-1 mediates lymphocyte binding using rotatory and flow chamber binding assays. VAP-1 cDNA transfected into an endothelial cell line, which does not bind lymphocytes, renders the cell line capable of binding lymphocytes in a shear-dependent manner. VAP-1 transfectants bound lymphocytes 5 times better than monocytes with a preference for T killer cells, and no specific granulocyte adherence was detectable. The binding is partially inhibited by anti-VAP-1 monoclonal antibodies or by blocking lymphocyte L-selectin and CD18 integrins, but not by inhibition of several other homing-associated molecules. In contrast, CD44 ligation on lymphocytes markedly upregulates their VAP-1-dependent adhesion, suggesting that the VAP-1 counterreceptor can be activated via CD44. The transfectant model also allowed us to perform detailed structure-function analyses of VAP-1. We show that the exposed integrin-binding motif RGD or the enzymatic activity is not indispensable for VAP-1-dependent adhesion. Together, these data show that VAP-1 can reconstitute the lymphocyte-endothelial adhesion cascade under shear and propose a critical role for VAP-1 in lymphocyte emigration from the blood.

The value of gene 'knock-out' for assessing the role of cell adhesion molecules in renal disease.

A number of approaches have been used to determine [3]. Notwithstanding this caveat, investigations the relative contributions of the four main classes of employing adhesion molecule-deficient animals have leukocyte adhesion molecules (selectins/selectin coun- significantly advanced our understanding of the functer-receptors, integrins/immunoglobulin superfamily tion of these leukocyte adhesion molecules in renal members) to the pathophysiology of autoimmune renal disease. Before discussing these studies, it is useful to inflammatory disease, allograft rejection, and ischaemic set the stage by briefly reviewing the paradigm of acute renal failure (ARF ). These strategies include leukocyte traYcking/immune cell infiltration as deteradministration of monoclonal antibodies, soluble mined using monoclonal antibodies. forms of adhesion molecules, synthetic oligosaccharides, and antisense oligonucleotides [1,2]. Most investigators have employed monoclonal antibodies against Paradigm of leukocyte traYcking as determined key adhesion epitopes. While this strategy has provided using monoclonal antibodies useful information in vivo and in vitro, certain methodological shortcomings mandate that any results must The movement of immune cells from the blood vessel be interpreted cautiously. The administration of monolumen to an inflammatory site occurs via an orches