Platelet interaction with bacteria

Platelets exert their main function in hemostasis and thrombosis, but they also are able to internalise infectious particles such as bacteria and viruses [1, 2] as well as inert particles like latex beads [3, 4]. This was initially interpreted as a passive passage of the particles through the platelet surface connected canalicular system (SCCS), or as a spreading of platelets over the particle [5]. Indeed the internalized particle often remains connected to the extracellular medium. A work recently performed in our laboratory using S. aurei and HIV [1], confirmed anterior studies [2] showing that platelets were able to interact directly with these micro-organisms by engulfing them. Contrary to the opinion expressed by White in his recent publication in this journal [5], we thought that this characteristic could confer to platelets a role in the protection and defense of the organism against any invasion by micro-organisms. Alternatively, by including infectious agents, platelets could contribute to the transport and the dissemination of infection in the organism. In favour to the first hypothesis, platelets contain microbicidal substances: a bactericidal peptide (PMP) has been found in the rabbit platelet granules [6] and components similar to PMP called thrombocidin were shown in the -granules of human platelets. Moreover, -granules are the storage place of many chemokines which are -thromboglobulin, platelet factor 4, neutrophil activating peptide-2, macrophage inflammatory protein-1 , PDGF, TGF [7]. They allow the interaction of platelets with other cells of the immune system in order to accelerate the immunizing responses. Platelets are a significant source of the chemokines RANTES (regulate upon activation normal T-cell expressed and secreted) [7, 8] which block viral infection by their capacity to enter in competition with viral particles, by fixation on their receptors [9]. Engulfment of foreign particles by platelets has been compared to phagocytosis. The phenomenom of phagocytosis involves the ingestion of particles, whereas pinocytosis involves the internalization of micelles and soluble molecules. There are several steps of phagocytosis, among which are adherence, pseudopodium extension, phagosome and phagolysosome formation. In that sense, platelet endocytosis is related to phagocytosis. However, the comparison between the ingestion phenomenon of platelets and phagocytes stops here, since the fate of the endocytosed microorganisms remains to be determined. Indeed phagocytes are able to ingest, digest, and kill microorganisms. Platelets are able to ingest foreign particles, and this property has been clearly demonstrated. To do so, they can extend pseudopodia filled with microfilaments and devoid of granules and mitochondria, like phagocytes do. Figure 1A shows that endocytosis within platelets is not a passive entrance of the foreign particle into the opening of the SCCS, but corresponds to an active platelet phenomenon. The two last steps, digestion and killing, are under investigation, and we are currently working on this topic. Partial digestion is suggested by contact with toxic platelet secretion products: Lewis and Maldonado [10] demonstrated earlier that platelet lysosomes were released along the engulfed particles, and we have shown that -granules could follow the same route (Figure 1B,C): indeed, immunolabelling for the -granule protein, fibrinogen, definitely shows that they are able to fuse with the compartment where bacteria are trapped. Moreover, it was shown that the phagocytic vacuole of phagocytes has specific properties, and that these properties are transmitted to the limiting membrane of secretory organelles which align and make contact with each other. Thus, neutrophil granules form necklaces whose content seems to flow towards the phagosome. In a similar way, we could observe