In vivo effects of lipopolysaccharide and TLR4 on platelet production and activity: Implications for thrombotic risk

Muthuvel Jayachandran, Gregory J. Brunn, Krzysztof Karnicki, Randall S. Miller, Whyte G. Owen, Virginia M Miller

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Gram-negative bacteria release LPS, which activates Toll-like-receptor-4 (TLR4) in the host, initiating an inflammatory response to infection. Infection increases risk for thrombosis. Platelets contribute to defense from infection and to thrombosis. Experiments were designed to determine whether LPS, through TLR4 signaling, affects platelet phenotype. Platelet responses in wild-type (WT) mice and mice that lack the TLR4 gene (dTLR4) were compared following a single nonlethal injection of LPS (0.2 mg/kg iv). Compared with WT mice, mice without TLR4 had fewer circulating platelets with lower RNA content and were less responsive to thrombin-activated expression of P-selectin but were equally sensitive to aggregation or ATP secretion. One week following the LPS injection, the time it takes for the circulating platelet pool to turnover, the number of circulating platelets, thrombin-induced expression of P-selectin, and collagen-activated aggregation were increased comparably in both groups of mice. Therefore, the change of the platelet pool to an activated phenotype 1 wk after a single exposure to LPS appears to arise from a process that is independent of TLR4. The persistence of the effect 1 wk after the injection suggests that the changes reflect an action of LPS on megakaryocytes and their platelet progeny rather than on circulating platelets, which would have been cleared.

Original languageEnglish (US)
Pages (from-to)429-433
Number of pages5
JournalJournal of Applied Physiology
Volume102
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Toll-Like Receptor 4
Lipopolysaccharides
Blood Platelets
P-Selectin
Thrombin
Injections
Thrombosis
Infection
Phenotype
Megakaryocytes
Gram-Negative Bacteria
Platelet Count
Collagen
Adenosine Triphosphate
RNA

Keywords

  • Aggregation
  • Infection
  • Megakaryocytes
  • P-selectin
  • Thrombosis

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

In vivo effects of lipopolysaccharide and TLR4 on platelet production and activity : Implications for thrombotic risk. / Jayachandran, Muthuvel; Brunn, Gregory J.; Karnicki, Krzysztof; Miller, Randall S.; Owen, Whyte G.; Miller, Virginia M.

In: Journal of Applied Physiology, Vol. 102, No. 1, 01.2007, p. 429-433.

Research output: Contribution to journalArticle

Jayachandran, Muthuvel ; Brunn, Gregory J. ; Karnicki, Krzysztof ; Miller, Randall S. ; Owen, Whyte G. ; Miller, Virginia M. / In vivo effects of lipopolysaccharide and TLR4 on platelet production and activity : Implications for thrombotic risk. In: Journal of Applied Physiology. 2007 ; Vol. 102, No. 1. pp. 429-433.
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