Platelet Toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-alpha production in vivo.
Toll-like receptors (TLRs) play a critical role in stimulating innate immunity by recognizing pathogen-associated molecular patterns (PAMPs) on invading microorganisms. Platelets also play a role in innate immunity, and we studied whether they express TLR. Results show that human and murine platelets variably expressed TLR2, TLR4, and TLR9 by flow cytometry and Western blotting. TLR4 expression was confirmed by demonstrating murine platelet binding to lipopolysaccharide (LPS). Thrombin activation of the platelets significantly enhanced the expression of TLR9, suggesting that at least some TLRs may derive from intracellular compartments. When LPS was administered to LPS-sensitive C3H/HeN and LPS-resistant C3H/HeJ mice, functional TLR4 expression in vivo was shown to be responsible for LPS-induced thrombocytopenia. However, when the C3H/HeN mice were first rendered thrombocytopenic by an antiplatelet antibody and then administered LPS, a significant reduction occurred in their ability to produce TNF-alpha. The decreased cytokine production in the thrombocytopenic mice was restored with platelet transfusion. These results suggest that platelets express various TLRs and that the functional significance of one of these, TLR4, appears to be a role in the modulation of LPS-induced thrombocytopenia and TNF-alpha production. This work implicates platelets as important mediators of innate immune responses against invading microorganisms.
Aslam
Rukhsana
R
Department of Laboratory Medicine and Pathobiology, St Michael's Hospital, 30 Bond St, Toronto, ON, Canada, M5B 1W8.
Speck
Edwin R
ER
Kim
Michael
M
Crow
Andrew R
AR
Bang
K W Annie
KW
Nestel
Frederick P
FP
Ni
Heyu
H
Lazarus
Alan H
AH
Freedman
John
J
Semple
John W
JW
D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics / Q000502:physiology; D008070:Lipopolysaccharides / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D013917:Thrombin / Q000378:metabolism; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
C061248:ITGB3 protein, human; D039661:Integrin beta3; D008070:Lipopolysaccharides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D013917:Thrombin