Basic mechanism of leukocyte migration.
Inflammation represents the consequence of capillary dilation with accumulation of fluid (edema) and the immigration of leukocytes. By the end of the last century, Metchnikoff noted the power of certain blood cells to move toward bacteria and foreign substances and ingest them. In fact, leukocytes adhere to the vascular endothelium, and subsequently leave the circulation by transendothelial migration driven by chemoattractants, a process known as diapedesis. Reversible adherence of leukocytes to endothelium, basement membranes, and other surfaces on which they crawl is an essential event in the establishment of inflammation, whose molecular basis is beginning to be understood. Inflammation can become chronic. The acute process, characterized by neutrophil infiltration and edema, gives way to a subsequent predominance of mononuclear phagocytes or lymphocytes. Insulin-dependent diabetes mellitus is the result of organ-specific autoimmune destruction of the insulin secreting beta-cells in the pancreatic islets of Langerhans. It has become evident that diabetes mellitus is a multifactorial disease caused in part by infiltrating T-lymphocytes, comparable to situations of inflammation. After presentation of the different effectors of the immune system and their fluxes through the body, this review will propose a general model of adhesion between leukocytes and endothelial cells. It will emphasize how the homing specificity of lymphocyte subsets to different lymphoid organs is ensured, and how leukocyte migration to sites of inflammation is regulated. Finally, general therapeutic perspectives based on adhesion molecules leading to cure or prevention of chronic inflammation will be discussed.
Imhof
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BA
Department of Pathology, CMU, Geneva.
Dunon
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D
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology* / Q000627:therapeutic use; D018925:Chemokines / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D016023:Integrins / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology
D015815:Cell Adhesion Molecules; D018925:Chemokines; D007136:Immunoglobulins; D016023:Integrins