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Platelets kill bacteria by bridging innate and adaptive immunity via platelet factor 4 and FcγRIIA
Essentials Human platelets specifically interact with IgG opsonized bacteria through FcγRIIA. Platelet factor 4 (PF4) binds to polyanions (P) and undergoes a conformational change. Anti‐PF4/P IgG opsonizes PF4‐coated Gram‐positive and Gram‐negative bacteria. Platelets specifically kill E.coli opsoni...
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Published in: | Journal of thrombosis and haemostasis 2018-06, Vol.16 (6), p.1187-1197 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Essentials
Human platelets specifically interact with IgG opsonized bacteria through FcγRIIA.
Platelet factor 4 (PF4) binds to polyanions (P) and undergoes a conformational change.
Anti‐PF4/P IgG opsonizes PF4‐coated Gram‐positive and Gram‐negative bacteria.
Platelets specifically kill E.coli opsonized with PF4 and human anti‐PF4/P IgG.
Summary
Background
Activated platelets release the chemokine platelet factor 4 (PF4) stored in their granules. PF4 binds to polyanions (P) on bacteria, undergoes a conformational change and exposes neoepitopes. These neoepitopes induce production of anti‐PF4/P antibodies. As PF4 binds to a variety of bacteria, anti‐PF4/P IgG can bind and opsonize several bacterial species.
Objective
Here we investigated whether platelets are able to kill bacteria directly after recognizing anti‐PF4/P IgG opsonized bacteria in the presence of PF4 via their FcγRIIA.
Methods
Using platelet‐bacteria suspension co‐culture experiments and micropatterns with immobilized viable bacteria, in combination with pharmacological inhibitors and human anti‐ PF4/P IgG we analyzed the role of platelet‐mediated killing of bacteria.
Results
In the presence of PF4, human anti‐PF4/P IgG and platelets, E. coli killing (> 50%) with colony forming units (CFU mL−1) 0.71 × 104 ± 0.19 was observed compared with controls incubated only with anti‐PF4/P IgG (CFU mL−1 3.4 × 104 ± 0.38). Blocking of platelet FcγRIIA using mAb IV.3 (CFU mL−1 2.5 × 104 ± 0.45), or integrin αIIbβ3 (CFU mL−1 2.26 × 104 ± 0.31), or disruption of cytoskeletal functions (CFU mL−1 2.7 × 104 ± 0.4) markedly reduced E. coli killing by this mechanism. Our observation of E. coli killing by platelets on micropatterned arrays is compatible with the model that platelets kill bacteria by covering them, actively concentrating them into the area under their granulomere and then releasing antimicrobial substances of platelet α‐granules site directed towards bacteria.
Conclusion
These findings collectively indicate that by bridging of innate and adaptive immune mechanisms, platelets and anti‐PF4/polyanion antibodies cooperate in an antibacterial host response. |
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ISSN: | 1538-7933 1538-7836 1538-7836 |
DOI: | 10.1111/jth.13955 |