An ultrastructural analysis of platelets, erythrocytes, white blood cells, and fibrin network in systemic lupus erythematosus

2016

Sci Rep

Self Cite

258

206

Complex interactions exist between cytokines, and the interleukin family plays a fundamental role in inflammation. Particularly circulating IL-1β, IL-6 and IL-8 are unregulated in systemic and chronic inflammatory conditions. Hypercoagulability is an important hallmark of inflammation, and these cytokines are critically involved in abnormal clot formation, erythrocyte pathology and platelet hyper-activation, and these three cytokines have known receptors on platelets. Although these cytokines are always unregulated in inflammation, we do not know how the individual cytokines act upon the structure of erythrocytes and platelets, and which of the viscoelastic clot parameters are changed. Here we study the effects of IL-1β, IL-6 and IL-8 at low physiological levels, representative of chronic inflammation, by using scanning electron microscopy and thromboelastography. All three interleukins caused the viscoelastic properties to display an increased hypercoagulability of whole blood and pathology of both erythrocytes and platelets. The most pronounced changes were noted where all three cytokines caused platelet hyper-activation and spreading. Erythrocyte structure was notably affected in the presence of IL-8, where the morphological changes resembled that typically seen in eryptosis (programmed cell death). We suggest that erythrocytes and platelets are particularly sensitive to cytokine presence, and that they are excellent health indicators.

Section: Resultsmentioning

confidence: 87%

“…In this paper, we include SEM micrographs taken as part of previous published papers, to support the in vitro results presented here4849505152. The inflammatory blood sample preparation was done as discussed for the healthy volunteers and also in the various papers itself.…”

Section: Methodsmentioning

confidence: 83%

Effects of IL-1β, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity

Bester

2016

Sci Rep

Self Cite

258

206

“…Although we have observed anomalies in the kinds of fibrin fibres produced in the plasma of patients with various inflammatory diseases (e.g. (Pretorius et al, 2011b;Pretorius et al, 2011c;Pretorius et al, 2012;Pretorius et al, 2013b;Pretorius et al, 2014a;Pretorius et al, 2014b;Kell and Pretorius, 2015b;Pretorius et al, 2015;Kell and Pretorius, 2016a)), this is the first time that we have observed fibrin amyloid in Parkinson's Disease, as assessed by thioflavin T staining and its sensitivity (and that of fibres observed in the SEM) to LBP. While fibrin and αsynuclein can coaggregate (Bhattacharjee and Bhattacharyya, 2014), it is especially notable that the thrombin-dependence and SEM fibre sizes tell us that the fibres we observe imply that they are essentially all made of fibrin.…”

Section: Discussionmentioning

confidence: 57%

Lipopolysaccharide-binding protein (LBP) can reverse the amyloid state of fibrin seen or induced in Parkinson’s disease: implications for its aetiology

Mbotwe

Kell

2017

Preprint

Self Cite

The thrombin-induced polymerisation of fibrinogen to form fibrin is well established as a late stage of blood clotting. In recent work, we showed that the presence of tiny amounts of bacterial lipopolysaccharide (LPS) could cause these clots to adopt an amyloid form, that could be observed via scanning electron microscopy (SEM) or via the fluorescence of thioflavin-T. This could be prevented by the prior addition of lipopolysaccharide-binding protein (LBP). We had also observed by SEM this unusual clotting in the blood of patients with Parkinson's disease (PD). We here show that this too can be prevented by LBP, thereby implicating such inflammatory microbial cell wall products in the aetiology of the disease. This may lead to novel treatment strategies in PD designed to target microbes and their products.

“…Upon activation, the platelets release their granular contents and merge with the fibrin fibers. Thus, platelets are seen extremely rarely in healthy whole blood after thrombin addition [12][13][14][15].…”

Section: Resultsmentioning

confidence: 99%

Deleterious mutation in the FYB gene is associated with congenital autosomal recessive small‐platelet thrombocytopenia

Levin

Koren

Journal of Thrombosis and Haemostasis

et al. 2015

Deleterious mutation in the FYB gene is associated with congenital autosomal recessive small-platelet thrombocytopenia. J Thromb Haemost 2015; 13, 1285-92.Summary. Background: The FYB gene encodes adhesion and degranulation-promoting adaptor protein (ADAP), a hematopoietic-specific protein involved in platelet activation, cell motility and proliferation, and integrin-mediated cell adhesion. No ADAP-related diseases have been described in humans, but ADAP-deficient mice have mild thrombocytopenia and increased rebleeding from tail wounds. Patients and methods: We studied a previously reported family of five children from two consanguineous sibships of Arab Christian descent affected with a novel autosomal recessive bleeding disorder with small-platelet thrombocytopenia. Homozygosity mapping and exome sequencing were used to identify the genetic lesion causing the disease phenotype on chromosome 5. Bone-marrow morphology and platelet function were analyzed. Platelets were characterized by scanning electron microscopy. Results: We identified a homozygous deleterious nonsense mutation, c.393G>A, in FYB. A reduced percentage of mature megakaryocytes was found in the bone marrow. Patients' platelets showed increased basal expression of P-selectin and PAC-1, and reduced increments of activation markers after stimulation with ADP, as detected by flow cytometry; they also showed reduced pseudopodium formation and the presence of trapped platelets between the fibrin fibers after thrombin addition, as observed on scanning electron microscopy. Conclusions: This is the first report of a disease caused by an FYB defect in humans, manifested by remarkable small-platelet thrombocytopenia and a significant bleeding tendency. The described phenotype shows ADAP to be important for normal platelet production, morphologic changes, and function. It is suggested that mutation analysis of this gene be included in the diagnosis of inherited thrombocytopenia.