Measuring and interpreting platelet-leukocyte aggregates

Finsterbusch, Michaela; Schrottmaier, Waltraud C.; Kral-Pointner, Julia B.; Salzmann, Manuel

doi:10.1080/09537104.2018.1430358

Cited by 121 publications

(108 citation statements)

References 129 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…The formation of platelet-leukocyte aggregates is now recognized as a sensitive marker of in vivo platelet activation and is a feature of inflammatory conditions 30 , 44 , 45 . These aggregates are mediated via multiple ligands and receptors including P-selectin which is translocated to the surface of activated platelets 44 .…”

Section: Discussionmentioning

confidence: 99%

Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis

Vardon-Bounes

Mémier

Marcaud

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Sepsis is associated with thrombocytopenia and microvascular thrombosis. Studies have described platelets implication in this pathology but their kinetics of activation and behavior remain poorly known. We show in a mouse model of peritonitis, the appearance of platelet-rich thrombi in organ microvessels and organ damage. Complementary methods are necessary to characterize platelet activation during sepsis as circulating soluble markers and platelet-monocyte aggregates revealed early platelet activation, while surface activation markers were detected at later stage. A microfluidic based ex-vivo thrombosis assay demonstrated that platelets from septic mice have a prothrombotic behavior at shear rate encountered in microvessels. Interestingly, we found that even though phosphoinositide-3-kinase β−deficient platelet mice formed less thrombi in liver microcirculation, peritoneal sepsis activates a platelet alternative pathway to compensate the otherwise mandatory role of this lipid-kinase to form stable thrombi at high shear rate. Platelets are rapidly activated during sepsis. Thrombocytopenia can be attributed in part to platelet-rich thrombi formation in capillaries and platelet-leukocytes interactions. Platelets from septic mice have a prothrombotic phenotype at a shear rate encountered in arterioles. Further studies are necessary to unravel molecular mechanisms leading to this prothrombotic state of platelets in order to guide the development of future treatments of polymicrobial sepsis.

show abstract

Section: Discussionmentioning

confidence: 99%

Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis

Vardon-Bounes

Mémier

Marcaud

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The investigation of the interaction between leukocytes and platelets was facilitated by the use of flow cytometric analysis and advanced microscopy techniques [30]. However, characteristics of PLAs in terms of size and number of platelets bound per leukocytes are not well defined.…”

Section: Inflammation and Platelet-leukocyte Interactionsmentioning

confidence: 99%

“…Images showing PLAs as investigated by flow cytometry, tissue section or live cell imaging were presented by Finsterbush et al in their review on platelet-leukocyte interactions in acute ischemic stroke, renal diseases, and hepatic as well as lung inflammation and infection. They suggested that PLAs within the circulation or locally at the sites of inflammation might represent markers of many thrombo-inflammatory diseases and could be used for the assessment of both thrombotic risk and disease progression [30]. Moreover, PLAs could be of great interest as markers of the modulation of thrombo-inflammation in patients receiving antithrombotic drugs in the setting of acute inflammation.…”

Section: Inflammation and Platelet-leukocyte Interactionsmentioning

confidence: 99%

“…As pointed out by Finsterbush et al in their review of the different methods to measure PLAs, to allow validating PLAs as a biomarker in the future, protocols for standardized sample preparation and robust reference values need to be established first. Histochemical and immunofluorescent imaging, coupled with advanced confocal or electron microscopy, provide high-resolution images to visualize platelet-leukocyte interactions within tissues [30]. Finsterbush et al also described different methods to visualize PLAs in vivo-intravital microscopy, which allows tracking cells in live animals over longer time periods in organs; intravenous administration of fluorochrome-conjugated monoclonal antibodies, and microfluidic assays to analyze platelet-leukocyte interaction dynamics under well-defined conditions, including investigation of human cells [30].…”

Section: Inflammation and Platelet-leukocyte Interactionsmentioning

confidence: 99%

See 1 more Smart Citation

Platelet Functions During Extracorporeal Membrane Oxygenation. Platelet–Leukocyte Aggregates Analyzed by Flow Cytometry as a Promising Tool to Monitor Platelet Activation

Mansour

Roussel

Gaussem

et al. 2020

JCM

View full text Add to dashboard Cite

Extracorporeal membrane oxygenation (ECMO) is an extracorporeal circulation used to manage patients with severe circulatory or respiratory failure. It is associated with both high bleeding and thrombosis risks, mainly as a result of biomaterial/blood interface phenomena, high shear stress, and complex inflammatory response involving the activation of coagulation and complement systems, endothelial cells, leukocytes, and platelets. Besides their critical role in hemostasis, platelets are important players in inflammatory reactions, especially due to their ability to bind and activate leukocytes. Hence, we reviewed studies on platelet function of ECMO patients. Moreover, we addressed the issue of platelet–leukocyte aggregates (PLAs), which is a key step in both platelet and leukocyte activation, and deserves to be investigated in these patients. A reduced expression of GPIb and GPVI was found under ECMO therapy, due to the shedding processes. However, defective platelet aggregation is inconsistently reported and is still not clearly defined. Due to the high susceptibility of PLAs to pre-analytical conditions, defining and strictly adhering to a rigorous laboratory methodology is essential for reliable and reproducible results, especially in the setting of complex inflammatory situations like ECMO. We provide results on sample preparation and flow cytometric whole blood evaluation of circulating PLAs.

show abstract

“…Psoriasis has long been viewed as an immunologically-driven disease, in which different leukocytes and T cells play important roles. Although platelet interactions with leukocytes have been reported for psoriasis mouse models and are typically found in many other inflammatory diseases (Ludwig et al, 2004;Tamagawa-Mineoka, 2015;Finsterbusch et al, 2018), a specific role for platelets in the skin lesions of psoriasis patients has not been noted. In agreement with the systemic inflammatory nature of psoriasis, we found platelet-PMN and –monocyte aggregates in the circulation to correlate with the disease in the skin.…”

Section: Discussionmentioning

confidence: 99%

Platelet-neutrophil aggregates promote skin pathology in psoriasis

Herster

Bittner

Cordrea

et al. 2019

Preprint

View full text Add to dashboard Cite

Psoriasis is a frequent systemic inflammatory autoimmune disease characterized primarily by skin lesions with massive infiltration of leukocytes but frequently also presents with cardiovascular comorbidities. Especially polymorphonuclear neutrophils (PMNs) abundantly infiltrate psoriatic skin but the cues that prompt PMNs to home to the skin are not well defined. To identify PMN surface receptors that may explain PMN skin homing in psoriasis patients, we screened 332 surface antigens on primary human blood PMNs from healthy donors and psoriasis patients. We identified platelet surface antigens as a defining feature of psoriasis PMNs, due to a significantly increased aggregation of neutrophils and platelets in the blood of psoriasis patients. Similarly, in the imiquimod-induced experimental in vivo model of psoriasis, disease induction promoted PMN-platelet aggregate formation. In psoriasis patients, disease directly correlated with blood platelet counts and platelets were detected in direct contact with PMNs in psoriatic but not healthy skin. Importantly, depletion of circulating platelets in vivo ameliorated disease severity significantly, indicating that the intimate relationship of PMNs and platelets may be relevant for psoriasis pathology and disease severity, and potentially for psoriasis-associated cardiovascular comorbidities.Key pointsHuman neutrophils in psoriasis patient blood show a distinct ‘platelet signature’ of surface antigensPlatelets congregate with neutrophils in psoriatic skin lesionsCirculating platelets contribute to psoriasis skin pathology

show abstract

Measuring and interpreting platelet-leukocyte aggregates

Cited by 121 publications

References 129 publications

Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis

Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis

Platelet Functions During Extracorporeal Membrane Oxygenation. Platelet–Leukocyte Aggregates Analyzed by Flow Cytometry as a Promising Tool to Monitor Platelet Activation

Platelet-neutrophil aggregates promote skin pathology in psoriasis

Contact Info

Product

Resources

About