Human plasmacytoid dendritic cells (pDC) are important modulators of adaptive T cell responses during viral infections. Recently, we found that human pDC produce the serine protease granzyme B (GrB), thereby regulating T cell proliferation in a GrB-dependent manner. In this study, we demonstrate that intrinsic GrB production by pDC is significantly inhibited in vitro and in vivo by clinically u...

The present common view about GRB origin is related to cosmology, what is based on statistical analysis, and on measurements of the redshifts in the GRB optical afterglows of long GRB. No correlation is found between redshifts, GRB spectrum, and total GRB fluence. Comparison of KONUS and BATSE data about statistics and hard X-ray lines is done, and some differences are noted. Hard gamma-ray aft...

BACKGROUND Granzyme B (GrB) is a serine protease, traditionally known as expressed by cytotoxic lymphocytes to induce target cell apoptosis. However, it is emerging that GrB, being also produced by a variety of normal and neoplastic cells and potentially acting on multiple targets, might represent a powerful regulator of a wide range of fundamental biological processes. We have previously shown...

The Large Aperture GRB Observatory (LAGO) is aiming at the detection of the high energy (around 100 GeV) component of Gamma Ray Bursts, using the single particle technique in arrays of Water Cherenkov Detectors (WCD) in high mountain sites (Chacaltaya, Bolivia, 5300 m a.s.l., Pico Espejo, Venezuela, 4750 m a.s.l., Sierra Negra, Mexico, 4650 m a.s.l). WCD at high altitude offer a unique possibil...

The serine protease granzyme B (GrB) induces apoptosis through both caspase-dependent and -independent multiple-cascade mechanisms. VEGF₁₂₁ binds to both VEGF receptor (VEGFR)-1 and VEGFR-2 receptors. We engineered a unique GrB/VEGF₁₂₁ fusion protein and characterized its properties in vitro and in vivo. Endothelial and tumor cell lines showed varying levels of sensitivity to GrB/VEGF₁₂₁ that c...

OBJECTIVE Granzyme B (GrB) is a pro-apoptotic serine protease that contributes to immune-mediated target cell apoptosis. However, during inflammation, GrB accumulates in the extracellular space, retains its activity, and is capable of cleaving extracellular matrix (ECM) proteins. Recent studies have implicated a pathogenic extracellular role for GrB in cardiovascular disease, yet the pathophysi...

We model the radio, optical, and X-ray emission for the afterglows of GRB 980703, 990123, 990510, and 991216, within the framework of relativistic jets, to determine their physical parameters. The models that yield acceptable fits to the data have jet energies mostly between 10 to 10 erg and initial opening angles between 1 and 4. The external medium density is uncertain by at least one order o...

With the successful launch of the Swift Gamma-ray Burst Explorer, a rich trove of early X-ray afterglow data has been collected by its on-board X-Ray Telescope (XRT). Some interesting features are emerging, including a distinct rapidly decaying component preceding the conventional afterglow component in many sources, a shallow decay component before the more “normal” decay component observed in...

Granzyme-mediated cell death is the main pathway for cytotoxic lymphocytes to kill virus-infected and tumour cells. A major player in this process is GrB (granzyme B), which triggers apoptosis in both caspase-dependent and caspase-independent pathways. A caspase-independent substrate of GrB is the highly conserved transmembrane receptor Notch1. The GrB cleavage sites in Notch1 and functional co...