an-vitro-assay-to-study-platelet-migration-using-rgd-functionalized

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers

Despite being anucleated cell fragments, platelets are now widely recognized for their multifaceted abilities. Not only do they form blood clots to ...

University Hospital, LMU Munich

Ludwig-Maximilians-University Munich

DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance

While hemostasis is the physiological process that prevents blood loss after vessel injury, thrombosis is often portrayed as a pathologic event involving blood coagulation and platelet aggregation eventually leading to vascular occlusion and tissue damage. However, recent work suggests that thrombosis can also be a physiological process, termed immunothrombosis, initiated by the innate immune system providing a first line of defense to locally control infection. Fibrin forms the structural basis of immunothrombotic clots and its assembly involves the concerted action of coagulation factors, platelets and leukocytes. Here, we summarize the cellular and molecular events that initiate fibrin formation during the innate immune response and discuss how aberrant activation of these pathways fosters pathologies associated with thrombosis, including disseminated intravascular coagulation and atherothrombosis.

Blood coagulation in immunothrombosis-At the frontline of intravascular immunity.

Blood platelets are critical for hemostasis and thrombosis and play diverse roles during immune responses. Despite these versatile tasks in mammalian biology, their skills on a cellular level are deemed limited, mainly consisting in rolling, adhesion, and aggregate formation. Here, we identify an unappreciated asset of platelets and show that adherent platelets use adhesion receptors to mechanically probe the adhesive substrate in their local microenvironment. When actomyosin-dependent traction forces overcome substrate resistance, platelets migrate and pile up the adhesive substrate together with any bound particulate material. They use this ability to act as cellular scavengers, scanning the vascular surface for potential invaders and collecting deposited bacteria. Microbe collection by migrating platelets boosts the activity of professional phagocytes, exacerbating inflammatory tissue injury in sepsis. This assigns platelets a central role in innate immune responses and identifies them as potential targets to dampen inflammatory tissue damage in clinical scenarios of severe systemic infection.

Migrating Platelets Are Mechano-scavengers that Collect and Bundle Bacteria.

Platelet homeostasis is essential for vascular integrity and immune defence. Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis) remains unclear. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFNα to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This pDC-dependent feedback loop is crucial for MK and platelet homeostasis at steady state and under stress. pDCs are best known for their ability to function as vigilant detectors of viral infection. We show that virus-induced activation of pDCs interferes with their function as homeostatic sensors of megakaryopoiesis. Consequently, activation of pDCs by SARS-CoV-2 leads to excessive megakaryopoiesis. Together, we identify a pDC-dependent homeostatic circuit that involves innate immune sensing and demand-adapted release of inflammatory mediators to maintain homeostasis of the megakaryocytic lineage.

Florian Gaertner

Department of Medicine I,
Institute of Surgical Research at the Walter Brendel Centre of Experimental Medicine

University Hospital, LMU Munich

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers

Florian Gaertner

Department of Medicine I,Institute of Surgical Research at the Walter Brendel Centre of Experimental Medicine

University Hospital, LMU Munich

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers

Department of Medicine I,
Institute of Surgical Research at the Walter Brendel Centre of Experimental Medicine