Table I. Nonhemostatic roles of platelets in infection and inflammation
Pathogen Reduction
Harboring of pathogens (viruses, bacteria, and parasites) (3, 4, 1216)
Clearance of bacterial infections (18)
Inhibiting growth of S. aureus via β-defensin and NET induction (19)
Bacterial trapping on surface Kupffer cells (5) and via hepatic and pulmonary NETs during sepsis (20)
Growth inhibition of malarial parasites via erythrocyte invasion (4)
Platelet TLRs
Pathogen detection (2)
TLR4: LPS-induced thrombocytopenia and TNF-α production (36), bacterial trapping via NETs in sepsis (6), possible role in thrombopoiesis (34, 43)
Platelet CD40L (CD154)
Inflammatory reactions via interaction with CD40 of vascular cells: release of adhesion molecules (45, 47, 48)
Triggering of T cell responses postinfection with L. monocytogenes (49, 50)
Binding of DCs: impairment of DC differentiation (51), suppression of DC proinflammatory cytokines (51), increase in DC IL-10 production (51)
Induction of B cell differentiation and Ab class-switching (54, 55)
Triggering of NF-κB activation in platelets (56)
Platelet MHC Class I
Intracellular MHC class I association with platelet α granules (75)
Presence of proteasome system with TAP molecules in platelets (75)
Platelet presentation of malarial peptides to malaria T cells: enhanced immunity toward parasite (76)
Platelet Cytokine/Chemokines
Many chemokines and cytokines involved in pro/anti-inflammatory pathways, including the immunosuppressant TGF-β, as well as chemokines PF-4, β-TG, RANTES, MIP-1α (81). For overview, see Ref. 2.
Platelet Transcriptomics
De novo synthesis of platelet molecules: significant amount of RNA (90104), contain molecular machinery for mRNA translation and ability to transfer RNA to other cells to regulate cellular function (101104)
Impact on health and disease (reviewed in Ref. 107)
Platelet activation via GPVI in autoimmune inflammatory arthritis forms PMPs (8)
LPS stimulation of platelet TLR4 forms PMPs in sepsis (125)
Increased IL-1 in PMPs indicates role in inflammation (8, 125)
Immune complexed bacterial components and epitopes of influenza viruses form PMPs via FcγRIIa (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, 117119, 128130)
Platelet Breakdown
Cross-reactive autoantibodies due to molecular mimicry between viral/bacterial Ags and platelet Ags (135139)
H. pylori ITP increased platelet count after eradication of H. pylori (140)
LPS enhancement of Ab-mediated platelet clearance in vitro and in vivo (37, 141)
CRP enhancement of Ab-mediated platelet clearance in vitro and in vivo (142)