Antimicrobial Host Defense

Novel Anti-bacterial Activities of β-defensin 1 in Human Platelets: Suppression of Pathogen Growth and Signaling of Neutrophil Extracellular Trap Formation

“…Megakaryocytes invest platelets with hBD-1 mRNA and hBD-1's basal protein expression in platelets indicates that it may also serve critical functions in defense against pathogens that gain access to the bloodstream. Platelets are immediate responders and the most abundant cell type to accumulate at sites of intravascular infection, which include infective endocarditis, suppurative thrombophlebitis, mycotic aneurysm, septic endocarditis, catheter and dialysis access site infections, and vascular prosthesis and stent infections [1] , [2] , [3] . Sequestration of bacteria and localized release of hBD-1 and other microbicidal proteins by platelets may limit the growth of pathogens at infected areas, providing time for leukocytes to gather and kill remaining bacteria.…”

“…To date, there are five distinct lineages of platelet microbicidal proteins (PMPs) that include: 1, platelet factor 4 and variants; 2, platelet basic protein and its proteolytic derivatives connective tissue activating peptide-3 and neutrophil activating peptide-2 (NAP-2); 3, r egulated upon a ctivation n ormal T cell e xpressed and s ecreted (RANTES); 4, thymosin β-4; and 5, fibrinopeptides [3] , [6] , [38] . In some cases, PMPs are cleaved into their active form by thrombin or other proteases in the immediate vicinity [3] . When platelets become activated they express surface P-selectin, which binds neutrophils, and release constitutively stored PMPs.…”

“…Like PMPs, we found that hBD-1 purified from platelets is capable of inhibiting the growth of S. aureus . PMPs permeabilize bacterial membranes in what appears to be a voltage-dependent manner [3] while defensins insert into bacterial membranes, inducing membrane depolarization and activation of lytic enzymes that permeabilize lipid bilayers [14] . Their precise modes of action at the bacterial cell wall, however, may not overlap completely.…”

“…It is well known that bacteria directly and indirectly induce platelet activation [2] , but emerging evidence indicates that platelets also alter the activity of bacteria via the release of microbicidal proteins. Collectively, they are termed platelet microbicidal proteins (PMPs), and include chemokines, fibrinopeptides, and thymosin β-4 [3] . Platelets deliver PMPs to sites of infection where they exert direct antimicrobial effects and potentiate the antibacterial properties of leukocytes [3] , [4] , [5] , [6] .…”

Could Microparticles Be the Universal Quality Indicator for Platelet Viability and Function?

“…There are no clear quality standards for PRP injections and the current existing variability has been described previously [72]. The mechanism by which PRP injections exert their healing properties is still not known but the abundance of growth factors present in platelets [73] and the bactericidal and other immune functions platelets possess [74] are thought to play a major role. In the context of this review it is conceivable that microparticles also play a role in these autologous treatments.…”