Platelet-derived CXC chemokines: old players in new games

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 concentr ations, these mediators appear to fulfill different and complementary tasks as first-line mediators in the recruitment and activation of leukocytes, a s well in the regulation of tissue repair. Whereas both proteins are struct urally closely related members of the CXC chemokine subfamily, they are sub ject 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 protei ns will act as stimulatory or inhibitory agents in neutrophil activation vi a 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 i nteraction with an unusual recepror(s) on leukocytes (a proteoglycan) appea rs to depend on its oligomeric stare. There is growing evidence that both c hemokines may interfere with each other at various regulatory levels to pro mote coordinated cell activation. Moreover, recent findings suggest novel a nd unexpected activities for these chemokines, which may extend our view on early host defense.