Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology.

Scientists and health professionals are exhaustively trying to contain the coronavirus disease 2019 (COVID-19) pandemic by elucidating viral invasion mechanisms, possible drugs to prevent viral infection/replication, and health cares to minimize individual exposure. Although neurological symptoms are being reported worldwide, neural acute and long-term consequences of SARS-CoV-2 are still unknown. COVID-19 complications are associated with exacerbated immunoinflammatory responses to SARS-CoV-2 invasion. In this scenario, pro-inflammatory factors are intensely released into the bloodstream, causing the so-called "cytokine storm". Both pro-inflammatory factors and viruses may cross the blood-brain barrier and enter the central nervous system, activating neuroinflammatory responses accompanied by hemorrhagic lesions and neuronal impairment, which are largely described processes in psychiatric disorders and neurodegenerative diseases. Therefore, SARS-CoV-2 infection could trigger and/or worse brain diseases. Moreover, patients with central nervous system disorders associated to neuroimmune activation (e.g. depression, Parkinson's and Alzheimer's disease) may present increased susceptibility to SARS-CoV-2 infection and/or achieve severe conditions. Elevated levels of extracellular ATP induced by SARS-CoV-2 infection may trigger hyperactivation of P2X7 receptors leading to NLRP3 inflammasome stimulation as a key mediator of neuroinvasion and consequent neuroinflammatory processes, as observed in psychiatric disorders and neurodegenerative diseases. In this context, P2X7 receptor antagonism could be a promising strategy to prevent or treat neurological complications in COVID-19 patients.

Using Cytometry for Investigation of Purinergic Signaling in Tumor-Associated Macrophages.

Tumor-associated macrophages are widely recognized for their importance in guiding pro-tumoral or antitumoral responses. Mediating inflammation or immunosuppression, these cells support many key events in cancer progression: cell growth, chemotaxis, invasiveness, angiogenesis and cell death. The communication between cells in the tumor microenvironment strongly relies on the secretion and recognition of several molecules, including damage-associated molecular patterns (DAMPs), such as adenosine triphosphate (ATP). Extracellular ATP (eATP) and its degradation products act as signaling molecules and have extensively described roles in immune response and inflammation, as well as in cancer biology. These multiple functions highlight the purinergic system as a promising target to investigate the interplay between macrophages and cancer cells. Here, we reviewed purinergic signaling pathways connecting cancer cells and macrophages, a yet poorly investigated field. Finally, we present a new tool for the characterization of macrophage phenotype within the tumor. Image cytometry emerges as a cutting-edge tool, capable of providing a broad set of information on cell morphology, expression of specific markers, and its cellular or subcellular localization, preserving cell-cell interactions within the tumor section and providing high statistical strength in small-sized experiments. Thus, image cytometry allows deeper investigation of tumor heterogeneity and interactions between these cells. © 2020 International Society for Advancement of Cytometry.