Emerging Roles for Platelets in Inflammation and Disease

Ferrer-Acosta, Yancy; Gonzalez, Marieli; Fernández, Mónica; Valance, Washington A

doi:10.4172/2332-0877.1000149

Cited by 16 publications

(16 citation statements)

References 81 publications

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“…Hence, the expression pattern of TLRs on platelets is unique in terms of their function and their role in the pathogenesis of inflammatory diseases including sepsis and other chronic inflammatory disorders. This is because platelets and TLRs expressed by these cells play a potential role in the process of inflammation, development of neutrophil extracellular traps (NETs) and several inflammatory diseases including atherosclerosis, sepsis [269][270][271][272][273]. For example, both platelet TLR4 and TLR2 are involved in its interaction with neutrophils causing the formation of a heterotypic complex with neutrophils [259,275].…”

Section: Platelets and Tlr Expression Patternmentioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

477

346

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The immune system is a very diverse system of the host that evolved during evolution to cope with various pathogens present in the vicinity of environmental surroundings inhabited by multicellular organisms ranging from achordates to chordates (including humans). For example, cells of immune system express various pattern recognition receptors (PRRs) that detect danger via recognizing specific pathogen-associated molecular patterns (PAMPs) and mount a specific immune response. Toll-like receptors (TLRs) are one of these PRRs expressed by various immune cells. However, they were first discovered in the Drosophila melanogaster (common fruit fly) as genes/proteins important in embryonic development and dorso-ventral body patterning/polarity. Till date, 13 different types of TLRs (TLR1-TLR13) have been discovered and described in mammals since the first discovery of TLR4 in humans in late 1997. This discovery of TLR4 in humans revolutionized the field of innate immunity and thus the immunology and host-pathogen interaction. Since then TLRs are found to be expressed on various immune cells and have been targeted for therapeutic drug development for various infectious and inflammatory diseases including cancer. Even, Single nucleotide polymorphisms (SNPs) among various TLR genes have been identified among the different human population and their association with susceptibility/resistance to certain infections and other inflammatory diseases. Thus, in the present review the current and future importance of TLRs in immunity, their pattern of expression among various immune cells along with TLR based therapeutic approach is reviewed.

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Section: Platelets and Tlr Expression Patternmentioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

477

346

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“…We suggest that TLT-1 interaction with fibrinogen is responsible for control of bronchoalveolar hemorrhage, as well as platelet modulation of neutrophil transmigration, and that elevated levels of TLT-1 in inflammatory conditions are biomarkers of dysregulation of these processes. HL112311), the National Institute of General Medical Sciences (IDeA 1.0×10 5 8.0×10 4 6.0×10 4 TLT-1 copy number…”

Section: Discussionmentioning

confidence: 99%

“…1 The role of platelets in hemostasis is well established, but in recent years a more holistic understanding has emerged of platelets as central effectors of inflammation and tissue repair, as well as coagulation. 4 Circumstantial evidence implicates platelets in both the etiology and resolution of ARDS, but the specific mechanisms are not well defined. 5 In animal models of ALI, platelets have been shown to exacerbate disease progression through activation of and recruitment of neutrophils to sites of endothelial damage.…”

Section: Introductionmentioning

confidence: 99%

Platelet-derived TLT-1 is a prognostic indicator in ALI/ARDS and prevents tissue damage in the lungs in a mouse model

Morales-Ortíz

Deal

Reyes

et al. 2018

Blood

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Abstract Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) affect >200 000 individuals yearly with a 40% mortality rate. Although platelets are implicated in the progression of ALI/ARDS, their exact role remains undefined. Triggering receptor expressed in myeloid cells (TREM)–like transcript 1 (TLT-1) is found on platelets, binds fibrinogen, and mediates clot formation. We hypothesized that platelets use TLT-1 to manage the progression of ALI/ARDS. Here we retrospectively measure plasma levels of soluble TLT-1 (sTLT-1) from the ARDS Network clinical trial and show that patients whose sTLT-1 levels were >1200 pg/mL had nearly twice the mortality risk as those with <1200 pg/mL (P < .001). After correcting for confounding factors such as creatinine levels, Acute Physiology And Chronic Health Evaluation III scores, age, platelet counts, and ventilation volume, sTLT-1 remains significant, suggesting that sTLT-1 is an independent prognostic factor (P < .0001). These data point to a role for TLT-1 during the progression of ALI/ARDS. We use a murine lipopolysaccharide-induced ALI model and demonstrate increased alveolar bleeding, aberrant neutrophil transmigration and accumulation associated with decreased fibrinogen deposition, and increased pulmonary tissue damage in the absence of TLT-1. The loss of TLT-1 resulted in an increased proportion of platelet-neutrophil conjugates (43.73 ± 24.75% vs 8.92 ± 2.4% in wild-type mice), which correlated with increased neutrophil death. Infusion of sTLT-1 restores normal fibrinogen deposition and reduces pulmonary hemorrhage by 40% (P ≤ .001) and tissue damage by 25% (P ≤ .001) in vivo. Our findings suggest that TLT-1 uses fibrinogen to govern the transition between inflammation and hemostasis and facilitate controlled leukocyte transmigration during the progression of ARDS.

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“…Omics methodologies have allowed elucidating mechanisms of pathogenesis for numerous disease-causing agents and facilitated discovery of disease biomarkers (biosignature) and response to prevention or therapy [20–24]. It has the potential to assess the effects of a particular factor on many molecules including thousands of mRNAs, proteins, metabolites, imprinting of genes, alternative splicing of mRNAs and mutations [22].…”

Section: Introductionmentioning

confidence: 99%

The Potential of Omics Technologies in Lyme Disease Biomarker Discovery and Early Detection

Badawi

2016

Infect Dis Ther

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Lyme borreliosis (LB) is the most prevalent arthropod-borne infectious disease in North America and many countries of the temperate Northern Hemisphere. It is associated with local and systemic manifestations and has persistent post-treatment health complications in some individuals. Innate and acquired immunity-related inflammation is likely to play a critical role in both host defense against Borrelia burgdorferi and disease severity. Large-scale analytical approaches to quantify gene expression (transcriptomics), proteins (proteomics) and metabolites (metabolomics) in LB have recently emerged with a potential to advance the development of disease biomarkers in early, disseminated and posttreatment disease stages. These technologies may permit defining the disease stage and facilitate its early detection to improve diagnosis. They will also likely allow elucidating the underlying molecular pathways to aid in identifying molecular targets for therapy. This article reviews the findings within the field of omics relevant to LB and its prospective utility in developing an array of biomarkers that can be employed in LB diagnosis and detection particularly at the early disease stages.

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Emerging Roles for Platelets in Inflammation and Disease

Cited by 16 publications

References 81 publications

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Platelet-derived TLT-1 is a prognostic indicator in ALI/ARDS and prevents tissue damage in the lungs in a mouse model

The Potential of Omics Technologies in Lyme Disease Biomarker Discovery and Early Detection

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