TY  - JOUR
U1  - Wissenschaftlicher Artikel
A1  - Wolff, Martina
A1  - Handtke, Stefan
A1  - Palankar, Raghavendra
A1  - Wesche, Jan
A1  - Kohler, Thomas P.
A1  - Kohler, Christian
A1  - Gruel, Yves
A1  - Hammerschmidt, Sven
A1  - Greinacher, Andreas
T1  - Activated platelets kill Staphylococcus aureus, but not Streptococcus pneumoniae—The role of FcγRIIa and platelet factor 4/heparinantibodies
JF  - Journal of Thrombosis and Haemostasis
N2  - Abstract

Background
Heparin induced thrombocytopenia (HIT) is likely a misdirected bacterial host defense mechanism. Platelet factor 4 (PF4) binds to polyanions on bacterial surfaces exposing neo‐epitopes to which HIT antibodies bind. Platelets are activated by the resulting immune complexes via FcγRIIA, release bactericidal substances, and kill Gram‐negative Escherichia coli.


Objectives
To assess the role of PF4, anti‐PF4/H antibodies and FcγRIIa in killing of Gram‐positive bacteria by platelets.


Methods
Binding of PF4 to protein‐A deficient Staphylococcus aureus (SA113Δspa) and non‐encapsulated Streptococcus pneumoniae (D39Δcps) and its conformational change were assessed by flow cytometry using monoclonal (KKO,5B9) and patient derived anti‐PF4/H antibodies. Killing of bacteria was quantified by counting colony forming units (cfu) after incubation with platelets or platelet releasate. Using flow cytometry, platelet activation (CD62P‐expression, PAC‐1 binding) and phosphatidylserine (PS)‐exposure were analyzed.


Results
Monoclonal and patient‐derived anti‐PF4/H antibodies bound in the presence of PF4 to both S. aureus and S. pneumoniae (1.6‐fold increased fluorescence signal for human anti‐PF4/H antibodies to 24.0‐fold increase for KKO). Staphylococcus aureus (5.5 × 104cfu/mL) was efficiently killed by platelets (2.7 × 104cfu/mL) or their releasate (2.9 × 104cfu/mL). Killing was not further enhanced by PF4 or anti‐PF4/H antibodies. Blocking FcγRIIa had no impact on killing of S. aureus by platelets. In contrast, S. pneumoniae was not killed by platelets or releasate. Instead, after incubation with pneumococci platelets were unresponsive to TRAP‐6 stimulation and exposed high levels of PS.


Conclusions
Anti‐PF4/H antibodies seem to have only a minor role for direct killing of Gram‐positive bacteria by platelets. Staphylococcus aureus is killed by platelets or platelet releasate. In contrast, S. pneumoniae affects platelet viability.
KW  - -
KW  - aPF4/H antibodies
KW  - FcγRIIa
KW  - PF4
KW  - platelets
Y1  - 2020
UN  - https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-41020
SN  - 1538-7836
SS  - 1538-7836
U6  - https://doi.org/10.1111/jth.14814
DO  - https://doi.org/10.1111/jth.14814
VL  - 18
IS  - 6
SP  - 1459
EP  - 1468
PB  - Wiley
CY  - Hoboken, New Jersey
ER  -