VCAM-1/alpha 4-integrin adhesion pathway: therapeutic target for allergic inflammatory disorders.
Lymphocyte recirculation and leukocyte extravasation involve a multistep process that is central to immune surveillance and the rapid response of white blood cells to sites of injury or infection. Interaction of vascular adhesion molecules (VCAM-1, ICAM-1, and selectins) with ligands on the leukocyte surface (integrins, carbohydrates, and mucin-like molecules) regulate diapedesis. The nature of an inflammatory stimulus ultimately determines the pattern of endothelial adhesion molecule expression and the avidity state of their counterreceptors, thus dictating to a large extent whether a subclass of leukocytes will play a dominant role in the immune response. Immunoglobulin superfamily member VCAM-1 recognizes alpha 4 beta 1 integrin, expressed on all leukocytes except neutrophils. Blockade or inhibition of VCAM-1/alpha 4 beta 1 interaction is expected to have therapeutic potential in treating various inflammatory disorders and autoimmune diseases since this adhesion pathway has a major influence on eosinophil, lymphocyte, and monocyte trafficking. This review summarizes some of the strategies that are currently used to selectively inhibit the VCAM-1/alpha 4 integrin pathway, including soluble VCAM-Ig fusion protein, peptide antagonists, antisense oligonucleotides, natural products, and neutralizing antibodies to VCAM-1 or alpha 4 integrin.
Foster
C A
CA
Department of General Dermatology, Sandoz Research Institute, Vienna, Austria.
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000517:prevention & control* / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000517:prevention & control* / Q000628:therapy*; D007167:Immunotherapy / Q000379:methods*; D039441:Integrin alpha4; D011485:Protein Binding / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4