Platelet response as a sentinel marker of toll-like receptor 4 activation in mice

Jayachandran, Muthuvel; Miller, Virginia M.; Brunn, Gregory J.; Owen, Whyte G.

doi:10.1016/j.thromres.2009.05.005

Cited by 8 publications

(12 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, in two mice that were necropsied immediately after death, we observed large pools of blood in the abdominal and thoracic cavities. Thrombocytopenia can occur quickly with loss of progenitors as mouse platelet half-life has been estimated to be 3.4 days (Jayachandran et al, 2010). …”

Section: Resultsmentioning

confidence: 99%

Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function

et al. 2017

View full text Add to dashboard Cite

BRCA1 is a well-known DNA repair pathway component and a tissue-specific tumor suppressor. However, its role in hematopoiesis is uncertain. Here we report that a cohort of patients heterozygous for BRCA1 mutations experienced more hematopoietic toxicity from chemotherapy than those with BRCA2 mutations. To test whether this reflects a requirement for BRCA1 in hematopoiesis, we generated mice with Brca1 mutations in hematopoietic cells. Mice homozygous for a null Brca1 mutation in the embryonic hematopoietic system (Vav1-iCre;Brca1F22–24/F22-24) developed hematopoietic defects in early adulthood that included reduced hematopoietic stem cells (HSCs). Although mice homozygous for a huBRCA1 knock-in allele (Brca1BRCA1/BRCA1) were normal, mice with a mutant huBRCA1/5382insC allele and a null allele (Mx1-Cre;Brca1F22-24/5382insC), had severe hematopoietic defects marked by a complete loss of hematopoietic stem and progenitor cells. Our data show that Brca1 is necessary for HSC maintenance and normal hematopoiesis, and that distinct mutations lead to different degrees of hematopoietic dysfunction.

show abstract

Section: Resultsmentioning

confidence: 99%

Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function

et al. 2017

View full text Add to dashboard Cite

show abstract

“…On the other hand, severe inflammation via TLR2 also regulates MK function that affects platelet production and function with enhanced GPIb and COX-2 protein expression [14]; however, no data has been published about TLR4 in this context. In former animal models, when mice were exposed to a sublethal/low dose of LPS for up to 1 week, platelets became gradually activated, showing high P-selectin surface positivity and a larger sensitivity to aggregation as a reflection to the action of LPS on MKs [31,32]. Very recently, ITGA2B (integrin subunit αIIb) expression has been found to be upregulated in circulating platelets during sepsis via dynamic trafficking of specific mRNA from MKs, and this was accompanied by increased production of integrin subunit αIIb and activation of integrin αIIbβ3 [22].…”

Section: Discussionmentioning

confidence: 99%

Reduced miR-26b Expression in Megakaryocytes and Platelets Contributes to Elevated Level of Platelet Activation Status in Sepsis

Szilágyi

Fejes

Póliska

et al. 2020

IJMS

View full text Add to dashboard Cite

In sepsis, platelets may become activated via toll-like receptors (TLRs), causing microvascular thrombosis. Megakaryocytes (MKs) also express these receptors; thus, severe infection may modulate thrombopoiesis. To explore the relevance of altered miRNAs in platelet activation upon sepsis, we first investigated sepsis-induced miRNA expression in platelets of septic patients. The effect of abnormal Dicer level on miRNA expression was also evaluated. miRNAs were profiled in septic vs. normal platelets using TaqMan Open Array. We validated platelet miR-26b with its target SELP (P-selectin) mRNA levels and correlated them with clinical outcomes. The impact of sepsis on MK transcriptome was analyzed in MEG-01 cells after lipopolysaccharide (LPS) treatment by RNA-seq. Sepsis-reduced miR-26b was further studied using Dicer1 siRNA and calpain inhibition in MEG-01 cells. Out of 390 platelet miRNAs detected, there were 121 significantly decreased, and 61 upregulated in sepsis vs. controls. Septic platelets showed attenuated miR-26b, which were associated with disease severity and mortality. SELP mRNA level was elevated in sepsis, especially in platelets with increased mean platelet volume, causing higher P-selectin expression. Downregulation of Dicer1 generated lower miR-26b with higher SELP mRNA, while calpeptin restored miR-26b in MEG-01 cells. In conclusion, decreased miR-26b in MKs and platelets contributes to an increased level of platelet activation status in sepsis.

show abstract

“…In addition, depending on the dose of LPS or type of bacterial infection, receptors other than TLR4 may be activated. Therefore, complement activation or cytokine-mediated mechanisms in vascular cells complicate unraveling mechanisms of LPS induced production of host MV (67)(68)(69).…”

Section: Host Processes Triggered By Bacterial Infection Direct Respomentioning

confidence: 99%

Microvesicles at the Crossroads Between Infection and Cardiovascular Diseases

Xiong

Miller

et al. 2012

Journal of Cardiovascular Pharmacology

Self Cite

View full text Add to dashboard Cite

Observational and experimental studies continue to support the association of infection and infection-stimulated inflammation with development of cardiovascular disease (CVD) including atherosclerosis and thrombosis. Microvesicles (MV) are heterogeneous populations of sealed membrane-derived vesicles shed into circulation by activated mammalian cells and/or pathogenic microbes that may represent an interface between bacterial/microbial infection and increased risk of CVD. This review evaluates how MV act to modulate and intersect immunological and inflammatory responses to infection with particular attention to progression of CVD. While infection-related stimuli provoke release of MV from blood and vascular cells, MV express phosphatidylserine (PS) and other procoagulant factors on their surface which initiate and amplify blood coagulation. In addition, MV mediate cell-cell adhesion which may stimulate production of pro-inflammatory cytokines in vascular cells, which in turn aggravate progression of CVD and propagate atherothrombosis. MV transfer membrane receptors, RNA and proteins among cells, and present auto-antigens from their cells of origin to proximal or remote target cells. Because MV harbor cell surface proteins and contain cytoplasmic components of the parent cell, they mediate biological messages and play a pivotal role in the crossroad between infection-stimulated inflammation and cardiovascular diseases.

show abstract

Platelet response as a sentinel marker of toll-like receptor 4 activation in mice

Cited by 8 publications

References 28 publications

Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function

Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function

Reduced miR-26b Expression in Megakaryocytes and Platelets Contributes to Elevated Level of Platelet Activation Status in Sepsis

Microvesicles at the Crossroads Between Infection and Cardiovascular Diseases

Contact Info

Product

Resources

About