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A Single in vivo Exposure to Low‐Dose LPS Decreases Platelet LifeSpan through TLR4 in Mice
Author(s) -
Jayachandran Muthuvel,
Hashimoto Kazunori,
Brunn Gregory J.,
Owen Whyte G.,
Miller Virginia M.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a183-b
Subject(s) - platelet , tlr4 , in vivo , platelet activation , lipopolysaccharide , p selectin , immunology , pharmacology , biology , chemistry , endocrinology , medicine , inflammation , microbiology and biotechnology
Infection increases propensity for thrombotic events. Gram negative pathogens release lipopolysaccharides (LPS), which initiate intracellular signaling cascades through activation of toll‐like‐receptor 4 (TLR4). Platelets contribute to defense from infection and to thrombosis, but little is known about how LPS affects platelet production, life span and reactivity. Platelet life span was determined by in vivo biotinylation in wild type (C57BL/10SnJ; WT) and TLR4 deficient (C57BL/10ScN; dTLR4) mice before and after a single intravenous injection of LPS (1ng – 500ng/25g body weight). Prior to LPS injection, the number of platelets and percentage of reticulated platelets in dTLR4 mice was less than in WT mice but there were no differences in platelet life span, indicating that loss of TLR4 affects platelet production and not life span. A single injection of LPS dose dependently increased percentages of P‐selectin positive platelets and of reticulated platelets but decreased the number of biotin positive platelets within 24hrs in WT but not in dTLR4 mice. Results suggest that LPS–simulated infection reduces life span of circulating platelet and increases production of more reactive (reticulated) platelets from megakaryocytes through TLR4 mechanisms. Thus, a single exposure to LPS represents a “priming” mechanism which could increase risk for thrombosis with infection. (Funded by NIH‐HL78638 and Mayo Fnd.)