In vivo effects of lipopolysaccharide and TLR4 on platelet production and activity: implications for thrombotic risk
| Autor: | Krzysztof Karnicki, Gregory J. Brunn, Randall S. Miller, Whyte G. Owen, Virginia M. Miller, Muthuvel Jayachandran |
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| Rok vydání: | 2007 |
| Předmět: |
Blood Platelets
Lipopolysaccharides medicine.medical_specialty Platelet Aggregation Lipopolysaccharide P-selectin Physiology Biology Hemostatics Mice chemistry.chemical_compound Megakaryocyte Risk Factors In vivo Physiology (medical) Internal medicine medicine Animals Secretion Platelet Cell Proliferation Mice Knockout Dose-Response Relationship Drug Tumor Necrosis Factor-alpha Thrombin Thrombosis Mice Inbred C57BL Toll-Like Receptor 4 P-Selectin Dose–response relationship medicine.anatomical_structure Endocrinology Gene Expression Regulation chemistry Immunology TLR4 Female lipids (amino acids peptides and proteins) Gene Deletion |
| Zdroj: | Journal of Applied Physiology. 102:429-433 |
| ISSN: | 1522-1601 8750-7587 |
| DOI: | 10.1152/japplphysiol.01576.2005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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