IMMUNOBIOLOGY Platelet Toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor- production in vivo

Toll-like receptors (TLRs) play a critical role in stimulating innate immunity by recognizing pathogen-associated molecu-lar patterns (PAMPs) on invading microor-ganisms. Platelets also play a role in innate immunity, and we studied whether they express TLR. Results show that hu-man and murine platelets variably ex-pressed TLR2, TLR4, and TLR9 by flow cytometry and Western blotting. TLR4 expression was confirmed by demonstrat-ing murine platelet binding to lipopolysac-charide (LPS). Thrombin activation of the platelets significantly enhanced the ex-pression of TLR9, suggesting that at least some TLRs may derive from intracellular compartments. When LPS was adminis-tered to LPS-sensitive C3H/HeN and LPS-resistant C3H/HeJ mice, functional TLR4 expression in vivo was shown to be re-sponsible for LPS-induced thrombocyto-penia. However, when the C3H/HeN mice were first rendered thrombocytopenic by an antiplatelet antibody and then adminis-tered LPS, a significant reduction oc-curred in their ability to produce TNF-. 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- production. This work implicates platelets as important mediators of innate immune responses against invading micro-organisms. (Blood. 2006;107:637-641) © 2006 by The American Society of Hematolog