title: Platelet-derived CXC chemokines: old players in new games.
abstract: Although platelet factor 4 (PF-4) and the beta-thromboglobulin (beta-TG) proteins represent the first chemokines to be discovered, their functional roles in host defense became clear only recently. Residing in platelets as storage proteins and becoming released into the blood at very high concentrations, these mediators appear to fulfill different and complementary tasks as first-line mediators in the recruitment and activation of leukocytes, as well in the regulation of tissue repair. Whereas both proteins are structurally closely related members of the CXC chemokine subfamily, they are subject to quite dissimilar regulatory mechanisms controlling their generation and their spectrum of biological activities. Thus, proteolytic processing of inactive precursors plays a decisive role in whether the beta-TG proteins will act as stimulatory or inhibitory agents in neutrophil activation via the G protein-coupled receptors CXCR-1 and 2. PF-4, existing as a single molecular form, is largely resistant to proteolytic modification, but its interaction with an unusual receptor(s) on leukocytes (a proteoglycan) appears to depend on its oligomeric state. There is growing evidence that both chemokines may interfere with each other at various regulatory levels to promote coordinated cell activation. Moreover, recent findings suggest novel and unexpected activities for these chemokines, which may extend our view on early host defense.
authors.affiliation: Department of Immunology and Cell Biology, Research Center Borstel, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Brandt
authors.forename: A
authors.initials: A
authors.lastname: Ludwig
authors.forename: F
authors.initials: F
authors.lastname: Petersen
authors.forename: H D
authors.initials: HD
authors.lastname: Flad
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000276:immunology*; D019743:Chemokines, CXC / Q000276:immunology*; D006801:Humans; D007109:Immunity; D008969:Molecular Sequence Data
chemical_list: D019743:Chemokines, CXC