The blood platelets contribution to innate host defense - what they have learned from their big brothers.
Bactericidal effects of blood platelets have been known for more than 120 years, but the underlying mechanisms are largely obscure. Keeping in mind structural and functional analogies of platelets to neutrophils, three different mechanisms are thinkable: Engulfment of pathogens, release of microbicidal proteins, and production of reactive oxygen species (ROS). Here, we focus on the release of ROS and a possible contribution of blood plasma and thrombin to the bactericidal effects. Killing of bacteria was evaluated by DNA fluorescence labeling and electron microscopy. Release of ROS by platelets was measured photometrically by cytochrome C and phenol red/peroxidase assays and was further evaluated by topological methods. We found that (i) platelets produce 1500 times less O(2) (-) and 4000 times less H(2)O(2) compared to neutrophils, (ii) ROS do not affect the killing rates, and (iii) no local enrichment of ROS was detectable. On the other hand, thrombin and plasma proteins with a molecular mass of >100 kDa are essential for bactericidal effects. We suggest that platelets contribute to the innate host defense by providing a catalytical surface for synthesis of thrombin. In the presence of a heat-instable plasma protein, thrombin may generate a strong bactericidal complex, which is only effective in close vicinity to the platelet membrane.
Zander
Dorit M W
DM
Institute of Anatomy, Center of Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany.
Klinger
Matthias
M
D001412:Bacillus subtilis / Q000276:immunology; D001424:Bacterial Infections / Q000097:blood* / Q000276:immunology; D001770:Blood Bactericidal Activity / Q000187:drug effects / Q000276:immunology*; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology*; D001798:Blood Proteins / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D007113:Immunity, Innate / Q000276:immunology; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000276:immunology; D009861:Onium Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D018709:Statistics, Nonparametric; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D001798:Blood Proteins; D009861:Onium Compounds; D017382:Reactive Oxygen Species; C007517:diphenyleneiodonium; D006861:Hydrogen Peroxide; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate