Glycoengineered anti-CD39 promotes anticancer responses by depleting suppressive cells and inhibiting angiogenesis in tumor models.

Immunosuppressive cells accumulating in the tumor microenvironment constitute a formidable barrier that interferes with current immunotherapeutic approaches. A unifying feature of these tumor-associated immune and vascular endothelial cells appears to be the elevated expression of ectonucleotidase CD39, which in tandem with ecto-5'-nucleotidase CD73, catalyzes the conversion of extracellular ATP into adenosine. We glycoengineered an afucosylated anti-CD39 IgG2c and tested this reagent in mouse melanoma and colorectal tumor models.

Vasculopathy in COVID-19.

COVID-19 is a primary respiratory illness that is frequently complicated by systemic involvement of the vasculature. Vascular involvement leads to an array of complications ranging from thrombosis to pulmonary edema secondary to loss of barrier function. This review will address the vasculopathy of COVID-19 with a focus on the role of the endothelium in orchestrating the systemic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Global deletion of NTPDase3 protects against diet-induced obesity by increasing basal energy metabolism.

Background: Ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3), also known as CD39L3, is the dominant ectonucleotidase expressed by beta cells in the islet of Langerhans and on nerves. NTPDase3 catalyzes the conversion of extracellular ATP and ADP to AMP and modulates purinergic signaling. Previous studies have shown that NTPDase3 decreases insulin release from beta-cells in vitro.

Structural and functional characterization of engineered bifunctional fusion proteins of CD39 and CD73 ectonucleotidases.

Extracellular diphosphate and triphosphate nucleotides are released from activated or injured cells to trigger vascular and immune P purinergic receptors, provoking inflammation and vascular thrombosis. These metabokines are scavenged by ectonucleoside triphosphate diphosphohydrolase-1 (E-NTPDase1 or CD39). Further degradation of the monophosphate nucleoside end products occurs by surface ecto-5'-nucleotidase (NMPase) or CD73.

Cationic zinc is required for factor XII recruitment and activation by stimulated platelets and for thrombus formation in vivo.

Background: Although divalent zinc (Zn ) is known to bind factor (F)XII and affect its sensitivity to autoactivation, little is known about the role of Zn in the binding of FXII to platelets, where FXII activation is thought to occur in vivo, and the function of Zn during thrombus formation following vascular injury remains poorly understood.

Objectives: To evaluate the role of Zn in platelet-dependent FXIIa generation.

Methods: FXII binding to platelets and FXII activation by stimulated platelets were assessed using flow cytometry and a platelet-dependent thrombin generation assay.