Bacillus anthracis peptidoglycan activates human platelets through FcγRII and complement

Abstract

Key Points PGN forms immune complexes with preexisting human anti-PGN antibodies to activate the classical complement pathway. Human platelets are activated by PGN–anti-PGN immune complexes through platelet FcγRIIa and through platelet binding C5b.

Inhibition of complement C5 protects against organ failure and reduces mortality in a baboon model of Escherichia coli sepsis

“…Indeed, we detected C3b on circulating aggregates of platelets and bacteria in baboons challenged with E. coli, suggesting that platelets and bacteria may be opsonized and cleared together, by blood and tissue phagocytes. We and others showed that C5b-9 deposition on platelets leads to platelet activation and aggregation (9,10). Future work should establish the relative contribution of activated complement to platelet and RBC clearance in sepsis.…”

“…C5a and C5b-9 increase the thrombogenicity of the blood by simultaneous induction of procoagulant (35) and antifibrinolytic proteins, and inhibition of natural anticoagulants (5). C5b-9 induces (5) or decrypts tissue factor (36), and induces exposure of phosphatidylserine on platelets to provide a catalytic surface for prothrombinase (9,10). C5a up-regulates tissue factor and PAI-1 (37) on monocytes, thereby enhancing blood thrombogenicity and decreasing dissolution of fibrin clots (38).…”

Nouvelle Cuisine: Platelets Served with Inflammation

“…The exposed PS, given its anionic properties, supports blood coagulation, although microparticles derived from platelets express modest levels of tissue factor (TF) and appear less procoagulant that do monocyte-derived microparticles, which express both PS and TF (113). In a recent study, Tersteeg et al (114) elegantly examined platelet activation Table I (8,125) Immune complexed bacterial components and epitopes of influenza viruses form PMPs via FcgRIIa (126,127) PMPs implicated in cell-cell communications via integrin, lactaderhin, and Del-1 (131, 132) PMP cargo consists of cytokines, chemokines, lipid mediators, enzymes, receptors, nucleic acids, autoantigens, transcription factors, mitochondria (103,(117)(118)(119)(128)(129)(130) under physiological flow and observed extremely long (up to 250 mm) membrane strands emerging from platelets, which is substantial considering their small size. These strands, called flow-induced protrusions, also expose PS, recruit neutrophils and monocytes (and not platelets), and appear to break off into PS + microparticles (114).…”

“…Platelets also participate in adaptive immunity through stimulation of FcgRIIA. Indeed, in immunized subjects, bacterial components and well-conserved epitopes expressed by influenza viruses are capable of forming immune complexes that activate FcgRIIA (126,127), leading to the formation of microparticles.…”

Platelets as immune-sensing cells

“…41 Several platelet surface receptors have been shown to trigger the formation of platelet microparticles such as GPVI during rheumatoid arthritis, 41 TLR4 signaling via lipopolysaccharide during sepsis, 42 and FcgRIIa, which may be targeted by immune complexes (of bacterial components or influenza viral epitopes). 43,44 The GPVI-and TLR4-mediated signals were also associated with increased IL-1 levels, illustrating their proinflammatory effects. Functionally, platelet microparticles can facilitate communication of platelets with other cells as they can carry a large variety of substances such as various cytokines or chemokines (eg, IL-1, RANTES), lipid mediators, enzymes, surface receptors like CD40L, autoantigens, transcription factors, and respiratory competent mitochondria, all of which can regulate immune functions.…”