PresentationHandouts
(9103-S)
Platelets as Fully Licensed Immune Cells
October 6, 2012 10:30 AM - 12:00 PM
Event Faculty List
Event Title: 9103-S: Platelets as Fully Licensed Immune CellsEvent Date: Saturday, October 6, 2012 Event Time: 10:30 AM to 12:00 PM
Director/Moderator/Speaker Olivier Garraud, MD PhD Director, the Auvergne-Loire Regional Blood Center Etablissement Francais du Sang [email protected] Disclosures: No
Speaker Eric Boilard, PhD Assistant professor Laval University, Rheumatology Immunology Research Center [email protected] Disclosures: No
Speaker Simon Panzer, MD Professor Medical University Vienna, AUSTRIA [email protected] Disclosures: No
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TRANSFUSION: PLATELETS CAN SENSE “DANGER” SIGNATURES AND SIGNAL “OTHER” IMMUNE CELLS TO RESPOND BY INFLAMMATION
Prof. Olivier GARRAUD MD PhD_Head, the Regional Auvergne-Loire Blood Center of the French National Blood Service (EFS)_Faculty of Medicine of Saint-Etienne, University of Lyon, France
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Blood collection: Platelet Component (PC)preparation
• Blood collection for making a PC (aphaeresis, buffy coat) inflicts cell lesions and some degree of activation (CD62P, sCD62P, CD63, cytokine production/release) mechanical stress, anticoagulant
• Storage in view of constituting a PC inventory (≤5 d) also inflicts platelet lesions(activation, cytokine production/release, emission of microparticles MPs etc.) contacts with plastics, gas exchanges, floatation in medium… chemical stress, ageing
-Cognasse F et al., Transfusion, 2006;46:1184-1189-Cognasse F et al., Transfusion, 2008a;48:809-813-Chavarin P et al., Vox Sang, 2011:100:247-249-Nguyen KA et al., Blood Transfus, 2012:July 12:1-2Further work either submitted or in preparation…
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Blood Transfusion: PC linked-hazards_1.Frequency
PCs: ~10% of deliveries;39.4% of incidents/accidents
Data from the French Hemovigilance 2011; ANSM 2012
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
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Blood Transfusion: PC linked-hazards_2.Severity
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
B cells
Plateletssupernatantor lysate
Activation:IL-6 release
ATR d5 (n=1) and d7 (n=3)Control d5 (n=10 and d7 (n=10)
Centrifugation
Plateletssupernatant
Plateletslysate
CD40L soluble
Supernatant Pellet
ATR +++ -
Control + ++
B cells: IL-6
PlateletSn
PelletSn
ATR +++ -
Ctl + ++
CD40-blocking antibodiessubstantiallyabrogated IL-6 secretion.
sCD40L…
CD40
PC transfusion linked hazards: Involvement of inflammatory cytokines
30 ART cases29 w/. sCD40L + IL-27 + Ox40L1 w/. sCD40L + IL-27
H. Hamzeh-Cognasse et al., submitted
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Platelets: Origin of the main molecules with relevance to transfusion_The 3 main sources of pltoriginating molecules:
1.Megakaryocytes 2.Absorbed from the environment (plasma)
3.Synthesized de novo (Weyrich et al.)
_The 3 main locations of pltoriginating molecules:
1.The membrane 2.The granules 3.The dense () granules
_The 3 main processes for gaining access to plt originating molecules:
1.Shedding(membrane)
2.Direct secretion(, )
3.Two time secretion (=> membrane => outside)()
_The 3 main categories of pltoriginating molecules:
1.Membrane GP 2.Signalosome Phospho-Proteins
3.Docked GP and other molecules
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
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Platelet, Signaling and beyondGarraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Platelet activation with LPS (E. coli, 1 µg/ML, 30 min)(picture by Charles-Antoine Arthaud, Saint-Etienne)
Dense Granules
Lysosomes
Chemokines
Alpha Granules
ADP, ATP, Ca++, Histamine, 5 HT…
RANTES, PF4, IL-8, ENA-78, MIP1a…Cell mitogens: PDGF, EGF, TGFß, VEGF…Hemostatic factors: Fibrinogen, PAI1, Plasminogen…Adhesion Proteins: Thrombospondin, vWF…Critical Ligands: GPVI, P-Selectin, CD40L/CD154
Platelets and Pathogen Recognition Receptors (PRR): the Toll like Receptors (TLRs)
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Platelet-TLR4 are functional and, upon LPS engagement, secrete or dock (differentially) an array of cytokines and the like
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Platelet1
Platelet2
TLR4LPS
1LPS
2
Signalisation 1MyD88, predominant
Signalisation 2TRIF, predominant
NFB
Cytokine SecretionProfile 1
Cytokine SecretionProfile 2
Activationsignalisation
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Platelets have the molecular machinery for signaling through TLR4
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Toll-like receptor 4 (TLR4) expression on platelet membranes. (A) TLR4 was detected by flow cytometry after gating on CD41+ cells. Platelets were unstimulated or stimulated (30 min, RT) with TRAP. One representative experiment is shown (n=10). (B) The mean percentage of CD41+ platelets also positive for TLR4, as determined by flow cytometry (mean ± SD from 10 independent experiments).
A
59% 70%
TLR4 expression gated on unstimulated platelet CD41+
TLR4 expression gated on TRAP stimulated platelet CD41+
59% 70%
TLR4 expression gated on unstimulated platelet CD41+
TLR4 expression gated on TRAP stimulated platelet CD41+
1%
Isotype control
TLR4
Human platelets can discriminate between various bacterial LPS isoforms via TLR4 signaling and differential cytokines secretionBerthetJ et al. , 2012 Clinical Immunology (in press)
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Platelets + LPS
Supernatant
PBMCs
Supernatant
TLR2 Signaling in plateletsGarraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Human platelet NF-kappa B links TLR2 and PAR1 to cytokine secretion
Pauline Damien1, FabriceCognasse1, 2, Bernard Payrastre3, Sherry L. Spinelli4, Neil Blumberg4, Richard P. Phipps4, Archibald McNicol 5, Bruno Pozzetto1, Olivier Garraud1, 2 and Hind Hamzeh-Cognasse1
Submitted for publication
*# *#
*# *#
*#
*# *#
*
*#
*# *#
*#
A
B
TRAP
Pam3CSK4
Both TRAP and TLR2-ligand triggering involve NFκB signaling but with different kinetics and intensity.
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TLR2 Signaling in plateletsGarraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Platelet Serotonin, sCD62p, RANTES and sCD40L released by platelets stimulated by TRAP or Pam3CSK4, with (w) or without (w/o) anti-human TLR2 blocking MoAb.
Serotonin
TLR2 Signaling in plateletsGarraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Serotonin, sCD62p, RANTES and sCD40L secretion levels from platelets stimulated by Pam3CSK4 (A, C, E and G) or TRAP (B, D, F and H) with (w) or without (w/o) the inhibitor of NF-κB (BAY 11-7082).
While TRAP induces the release of dense and α-granule content, TLR2-ligand selectively and specificallypromotes the release of α-granule content.
_Platelets: Other Sensors of Danger and Receptors
After: Flaujac C et al., CellMol Life Sci, 2010;67:545-556 (Review)
Platelet
FcR()
CR
PRR
TLR (ligands = PAMP)
Defensins (ligands =DAMP tissue damageand/or repair)
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
a2b1
CR2
CCR1CCR3CCR4CXCR4
DC-SIGN
GPVI
a2b3CARCLEC2
VP4 (Rotavirus)
EBV
HIVHIV, Lentivirus
HCV
AdenovirusHantavirus
CoxsackieHIV
Other viruses, bacteriaeOther types of microbes
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Hypothesis: Blood processing for constituting PCs may harm cells and present as a “danger”
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Platelets engage mutual interactions with leukocytes: relevance in transfusion
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Platelet binding to PBMC increases upon platelet storagePlatelets bound to B cells, monocytes and T cells induce their activation.
Platelets and B lymphocytes were mutually activated; after a 3-day incubation with platelets, differentiated B cells increased their in vitro production of IgG1, IgG2, IgG3, but not IgG4, IgA, IgM
The release of platelet-derived nucleotidic molecules is inhibited upon binding of platelets to DC, thus limiting DC activation and promoting a tolerogenic phenotype
Physiopathology of PC linked-inflammation:_Acute Transfusion Reactions (ATRs)• 1. Non Hemolytic Febrile Transfusion Reactions (NHFTRs)
Predictive value of cytokine secretion in the platelet component in ATRs
Observations in 65 non-TRALI cases (grades 3 & 4; accountability 2 and over)
Nguyen KA el al, in preparation for publication
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
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• 2. Transfusion Related Acute Lung Injury (TRALI)
Physiopathology of PC linked-inflammation:_Acute Transfusion Reactions (ATRs)
Silliman C, Blumberg N, Phipps R, et al. Blood (2006)
Blood Component
Fresh plasma (healthy)
Platelets from whole blood
Platelets collected by apheresis
CD40 Ligand levels (ng/ml)in blood products
No TRALI TRALI
0.01 ± 0.003 N/A
7.9 ± 1.114.0 ± 3.0
11.8±0.82 44.7 ± 4.5
Acute pulmonary insufficiency induced by transfusion and involving neutrophil damage to endothelium; Cohort study -
534 platelet transfusions
Blumberg/Heal/Phipps Transfusion 2006;46:1813
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
• Platelets activate DCs and interfere with T cells, B cells, monocytes etc.
• Platelets would be able to function as APCs (Chapman LM, J Immunol2012;189:916-923), though debatable
• Physiological inflammation is instrumental in assisting APC function (cartoon)
• Transfusion represents an inflammatory situation (Transfus ClinBiol, special issue, 2012;19:81-138)
• HLA Ags, HPA Ags; ITP; FNAIT: role of cytokines during pregnancy?
• Do transfused platelets favor APC of their own Ags?
Physiopathology of PC linked-inflammation:_Speculation: A role in Allo-Immunization
Capture
SynthesisDegradation
CaptureSignalingActivation
SynthesisDegradation
-Cytokines (pro-inflamm.)-MHC molecules
s
-Peptides (to be presented)-Debris (inflammatory)
Antigen Presenting Cell
T cell
Th1
Th1
Th1
B
Mo
Inflammatory cytokines and products
Th2
B
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Conclusions and perspectives
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Therapeutic principle (Platelets)
+Cytokines, Chemokines, BiologicalResponse Modifiers,&Residual plasma, anticoagulant, etc.
Donor Plateletsin the Recipient
Circulation Arborescence
RecipientImmune Cell
Foreign ¢ (platelets)
Stressed Platelets
_Platelet DAMP_Immune ¢ Sensor/Defensin
Infused Donor Platelets maysignal Sensors in the Recipient Inflammation
(+)?: healing
(-): ATR + immunization
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In summary:• Platelets are fully licensed immune cells because they have the
main 4 properties that entitle them for this characteristics (Garraud,
Hamzeh-Cognasse, Cognasse, Pozzetto, Cavaillon, Weyrich & Semple: Review submitted for publication).• Expression of non-mutated receptors => bind pathogen or pathogen
derived structures• Ability to ingest pathogens• Capacity of secreting cytokines, chemokines, inflammation mediators• Capacity of activating a signaling machinery in a polarized manner
• It has been suggested that they present Ag• They interact w/ innate immune cells from the environment and
w/ adaptive immune cells, and alter their physiology• They are involved potentially in physiological inflammation and
certainly in pathological inflammation• More?
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Main collaborations
• University of Louvain, Clinics of Mont‐Godinne, Belgium
• University of Winnipeg, CN
• Etablissement Français du Sang (several other regions)
• Institut National de la Transfusion Sanguine
• CHU de Saint‐Etienne
• Université de Lyon
• INSERM (Lyon, Paris, Toulouse)
• Insitut Cochin, INSERM & CNRS, Paris
• University of Monastir and University Hospitals and Blood Banks in of Sousse, Monastir and Tunis; & the Pasteur Institute in Tunis.
• King Saudi University, Saudi Arabia; the Assiut University, Egypt
• Special thanks to advisers: Pr Andy Weyrich, Salt Lake City, USA; Pr John Semple, Toronto, CN; Prs Neil Blumberand Rick Phipps, and Dr S. Spinelli, Rochester‐NY, USA; Pr Larry Corash, University of California, San Francisco, USA; Pr B. Payrastre, CNRS, Toulouse, FR
Main Fundings
• Etablissement Français du sang
• Université Jean‐Monnet de Saint‐Etienne
• Association Recherche Transfusion
• Association les Amis de Rémi
• Région Rhône‐Alpes (C‐MIRA) – partnershipwith the University of Monastir in Tunisia
Garraud O, Cognasse F, Hamzeh-Cognasse H et al. Saint-Etienne, France — AABB Boston 2012
Merci pour votre attentionFabrice COGNASSE,
PhD
Sandrine LARADI, Pharm D, PhDHind HAMZEH-COGNASSE, PhD
Patricia CHAVARIN, MD
Olivier GARRAUDMD, PhD, Prof.Kim A NGUYEN
MD, PhD Student
Missing: Vincent BOST, MD (clinical investigations) & Antoine PRIGENT (MD, PhD Student)
ChakerALOUI,PhD Student)
PaulineDamien, PhD student
Pr. Bruno POZZETTOHead of the Univ. group
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Platelet functions beyond hemostasis
Simon Panzer, MD
Medical University Vienna, [email protected]
Disclosure
Unfortunately, none
platelet -activation, -function
Alan Michelson 2005
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subendothelial matrix
Ib IbIa/IIa
IIb/IIIa*Ib
Ia/IIaVI/Fc
IIb/IIIa*
primary adhesion
firm adhesion
activation
vWF
endothelial cell
collagen
Ib IbIb
fibrinogen
endothelial cell
blood flow
Kehrel BE, with permssion
platelets’ hemostasis
subendothelial matrixvWF
endothelial cells
endothelial cells
collagen
IIb/IIIa*Ib
fibrinogen
P-selectin TSP
recruitment
ADP Thromboxan A2
MMP
ADPadhesion proteins growth factors
spreadinggranule
secretion
IIb/IIIa*
Kehrel BE, with permssion
thrombin
platelets’ hemostasis
Platelets in Love
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PMNL
subendothelial matrix
endothelial cell‐
endothelial cell
collagen
monocyte
aggregation + recruitment of leukocytes Kehrel BE, with permssion
the clot
Platelets as targets of an immune response
(Auto)Immune Thrombocytopenia
antibody‐mediated, T cell mediated, reactive oxygen species
Allo‐Immune: NAIT, Refractoriness to platelet transfusions, Post‐transfusion Purpura
antibody‐mediated
platelets contain what you need for life, or will find the relevant source
you
Platelets store bioactive mediators
Platelets contain mRNA to generate their own proteins
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beyond hemostasis
cancer proliferation
viral spreading, promote cytotoxic T cells
host defense against microorganisms
infection/inflammation ‐ thromboembolism
Drawings from Bizzozero‘s original paper (1882)
„every time when a vascular wall is damaged ... arrest of whiteblood corpuscles represents a secondary phenomenon and may, perhaps, be caused by increasedadhesive properties of bloodplatelets whereby these cellsreact with white blood corpuscleswhich have been brought intocontact with them by bloodcirculation“
Bizzozero (1882)
key: platelets adhering to leukocytes
1963
Bolton F G & Boyd JPlatelet adherence to polymorphs. Br. Med. J. 2, 747 (1963)
Crome P E & Barkhan PPlatelet adherence to polymorphs. Br. Med. J. 2, 871 (1963)
Field E J & McLeod IPlatelet adherence to polymorphs. Br. Med. J. 2, 388 (1963)
„We cannot relate this phenomenon to anyfunctional abnormality of the blood nor to thepatient‘s symptons, but we think the appearance issingular enough to be worth reporting.“
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putative adhesion molecules involved in platelet adhesion to leucocytes
platelets leukocytes
P-selectin PSGL-1
GPIIb/IIIa, GPIb, Jam-3 Mac-1
CD40L CD40
ICAM-2 LFA-1
CD47 CD36
CD45 CD45CD45
CD45
CD61
CD61
CD61
CD61
Granulocytes Monocytes Lymphocytes Platelets
w/o agonistplatelets adhering to leukocytes
resting activated
Human platelet antigen-1a antibodies induce the release of the chemokine RANTES from human platelets
Dettke M et al, Vox Sang 2001; 81:199
the release of RANTES is FcII dependent
RANTES from platelets, can bind in flamed endothelium, forming a bridge between mononuclear cells and the vascular wall. RANTES also induces rapid intracellular signaling events in leukocytes and, in monocytes, directly signals to gene expression pathways that control in fammation
alloantibodies induce cytokine release
Platelet activation can result in release of multiple and diverse soluble mediators with pleiotropic functions in inflammation
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adhesion molecules involved in plateletadhesion to leucocytes
platelets ligands leucocytes
P-selectin - PSGL-1
GPIIb/IIIa fibrinogen Mac-1 (CD11b/CD18)
or CD11c/CD18GPIIb/IIIa fibronectin
vitronectinthrombospondin
Mac-1 (CD11b/CD18)
CD40L - CD40
ICAM-2 - LFA-1 (CD11a/CD18)
GPIbα high molecular weight kininogen
Mac-1 (CD11b/CD18)
Jam-3 - Mac-1 (CD11b/CD18)
CD47 thrombospondin CD36
New Links Between Inflammation and Thrombosis
Wagner DD, ATVB 2005;25:1321
.
the interplay of platelets and leukocytes in thrombosis and inflammation
‐ platelet P‐selectin contributes significantly to atherosclerotic lesion growth
‐ platelet P‐selctin activates endothelial cells inducing leukocyte rolling
‐ P‐selectin regulates fibrin deposition
‐ P‐selectin induces microparticles from monocytes (tissue factor)
‐ platelet P‐selectin capture leukocyte microparticles (via PSGL‐1) to thrombi (TF)
soluble CD40L (CD154) comes from platelets
regulation of adaptive immune resonse
supports B cell differentiation, Ig‐switchaugment CD8+ T cell response
platelet CD40L promotes DC maturationreduction of proinflammatory cytokines
Sprague DL et al, Immunol Res 2007;39:185
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Platelet components associated with acute transfusion reactions: the role of platelet-derived
soluble CD40 ligandCognasse F et al, Blood 2008; 112:4779
sCD40L in platelet concentrates (PCs) is associated with clinical Acute Transfusion Reaction through B‐cell responses as an indication of pathophysiologic function. There is a sustained role for PC‐derived sCD40L.
Toll-like receptors (TLR)
pattern recognition receptors (PRR): recognize molecules broadly shared by pathogens distinguishable from host molecules, referred to as pathogen-associated molecular patterns (PAMPs)
TLR on human platelets
Aslam R et al Platelets 2004; 15: 267Shiraki R et al Thromb Res 2004; 113:379Andonegui C et al Blood 2005; 106:2417Cognasse F et al Immunol Cell Biol 2005; 88:196
thrombin activated platelets increaselevels of TLR4 and TLR9
resting thrombin activated resting thrombin activated
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Platelet Toll‐like receptor expression modulates lipopolysaccharide‐induced thrombocytopenia and tumor necrosis factor‐alpha production in
vivoAslam R et al, Blood 2006;107:637
bridging infection with thrombosis:
Thrombin and LPS induce TLR 4 and TLR 9
Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic bloodClark SR et al, Nature Medicine 2007; 13: 463
Platelets and the immune continuumSemple JW et al Nature Reviews 2011; 11: 265
Bacteria bind to platelet TLR4 and are killed directly or by “trapping” provide professional phagocytosisPlatelet TLR4 presents LPS to neutrophils promoting their activation
Lipopolysaccharide from enterohemorrhagicEscherichia coli binds to platelets through TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome.Stahl AL et al Blood 2006; 108: 167
Platelet TLR4 binds only to LPS of E.colienterohaemorrhagica if associated with haemolyticuremic syndrome (HUS), but not not if infection is not leading to HUS. This mechanism may explain platelet consumption in HUS
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Human neutrophil alpha‐defensins induceformation of fibrinogen and thrombospondin‐1 amyloid‐like structures and activate platelets via glycoprotein IIb/IIIa.HORN M et al, J Thromb Haemost 2012; 10: 647
Defensins activate platelets and induce platelet apoptosis by formation of amyloid-like proteins. As these structures entrapped bacteria and fungi, they might reflect an additional function of HNPs in host defense. The described mechanism links again thrombosis and infection.
Staphylococcal extracellular adherence protein induces platelet activation by stimulation of thiolisomerasesBertling et al, ATVB 2012; 32: 1979
staphylococcus aureus can induce platelet aggregationsurface-located thiol isomerases play an important role in platelet activation
staphylococcal extracellular adherence protein induced thiol isomerase-dependent
glycoprotein IIb/IIIa activation, granule secretion, platelet aggregation
The prothrombotic features of a microbial secreted protein could explain infection-associated thrombosis
Defensins kill bacteria
platelets’ granule: thrombocidinsPlatelets kill intraerythrocytic malarial parasites and mediate survival to infectionMcMorran B J et al, Science 2009; 323: 797
platelets can kill parasites in vitro and in miceplatelet‐deficient mice are more likely to die from malaria than mice with normal platelet countsa single dose of aspirin may interfere with platelets sufficiently to prevent their killing power
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selection for further readings
The evolving role of platelets in inflammationWeyrich AS, J Thromb Haemost 2003; 1:1897
New links between inflammation and thrombosisWagner DD, ATVB 2005; 25:1321
Platelets and innate immunitySemple JW, Cell Mol Life Science 2010; 67:499
Platelets and the immune continuumSemple JW, Nature Rev Immunol 2011; 11:264
Bidirectional crosstalk between platelets and monocytes initiated by Toll-like receptor: An important step in the early defense against fungal infections?Bruserud O, Platelets 2012; PMID: 22646762
PlateletsMichelson AD Elsevier, second edition 2007
summary of platelets’ functions
• ensure haemostasis
‐ clot formation
‐ initiation/interaction of plasma coagulation
‐ secure the vascular integrity
‐ vessel repair
• surveillance‐ Inflammation
‐ bridging innate and adaptive immune response
‐ Fully licensed immune cells
inspired by work and discussions
John Semple, Toronto, Canada
Andy Weyrich, Salt Lake City, USA
Beate Kehrel, Muenster, Germany
Olivier Garraud, Lyon, France
Alan Michelson, Boston, USA
Platelet functions beyond hemostasis
This presentation will comprise selected topics showing platelets’ function beyond haemostasis with emphasis on the interaction of platelet with leukocytes, how platelets bridge innate and adaptive immunoresponses and platelets as a killing machinery of bacteria. The interaction between platelets with bacteria via platelets’ Toll-like receptors shall illustrate how infections can become procoagulatory.
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