Platelet-derived chemokines: pathophysiology and therapeutic aspects.
The identification of chemokines in blood platelets has strengthened our view of these cells as participants in immune host defense. Platelet chemokines representing prestored and rapidly releasable proteins may play a major role as first-line inflammatory mediators. This is evident from their capability to recruit early inflammatory cells such as neutrophil granulocytes and monocytes and even to exhibit direct antimicrobial activity. However, insight is growing that platelet chemokines may be also long-term regulators, e.g., by activating T lymphocytes, by modulating the formation of endothelium and even thrombocytopoiesis itself. This review deals with the individual and cooperative functionality of platelet chemokines, as well as their potential as a basis for therapeutic intervention in the pathology of inflammation, infection, allergy and tumors. Within this context, therapeutic strategies based on the use of antibodies, modified chemokines, chemokine-binding proteins and chemokine receptor antagonists as well as first clinical studies will be addressed.
Flad
Hans-Dieter
HD
Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany. hdflad@fz-borstel.de
Brandt
Ernst
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001792:Blood Platelets / Q000502:physiology*; D018925:Chemokines / Q000276:immunology / Q000378:metabolism*; D002633:Chemotaxis; D006706:Homeostasis; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D007239:Infections / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D009000:Monocytes / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D020556:Neutrophil Infiltration; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000378:metabolism; D034061:Thrombopoiesis
D000911:Antibodies, Monoclonal; D018925:Chemokines; D019707:Receptors, Chemokine