Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe forms of dengue virus disease, known as dengue hemorrhagic fever and dengue shock syndrome, result from an aberrant immune response involving antibody-dependent enhancement of infection, thrombocytopenia, and a loss of vascular integrity, culminating in hemorrhage, shock, and in some cases, death. Several studies have indicated that dengue virus infection results in the induction of apoptosis of certain cells believed to be contributory players in dengue pathogenesis. However, none have specifically examined the role of antibody enhancement in the context of induction of apoptosis. Here, we show that antibody-enhanced dengue virus infection of the FcR-bearing mast cell/basophil KU812 cell line results in a massive induction of apoptosis. Confocal microscopy and flow cytometry indicate two distinct subpopulations consisting of productively infected cells and apoptotic-uninfected bystanders. Apoptosis was found to be caspase-dependent, involving global caspase activation and cleavage of poly-ADP-ribose polymerase (PARP) and D4-guanosine diphosphate dissociation inhibitor (D4-GDI). Additional FcR-bearing cells, including K562, U937, and human mast cell 1 (HMC-1), were analyzed for apoptosis induction following infection. Although all cells displayed high susceptibility to antibody-enhanced dengue virus infection, only cells of a mast cell phenotype (KU812 and HMC-1) were found to undergo apoptosis. Dengue-induced apoptosis of KU812 cells was shown to require antibody-enhanced dengue virus infection by blockade of FcgammaRII. Transfection of KU812 cells with L-SIGN/DC-SIGNR was able to overcome the requirement for antibody enhancement with regard to dengue virus infection and apoptosis.
 ...
PMID:Dramatic caspase-dependent apoptosis in antibody-enhanced dengue virus infection of human mast cells. 1880 35

Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). DHF/DSS patients have been reported to have increased levels of urinary histamine, chymase, and tryptase, which are major granule-associated mediators from mast cells. Previous studies also showed that DENV-infected human mast cells induce production of proinflammatory cytokines and chemokines, suggesting a role played by mast cells in vascular perturbation as well as leukocyte recruitment. In this study, we show that DENV but not UV-inactivated DENV enhanced degranulation of mast cells and production of chemokines (MCP-1, RANTES, and IP-10) in a mouse model. We have previously shown that antibodies (Abs) against a modified DENV nonstructural protein 1 (NS1), designated DJ NS1, provide protection in mice against DENV challenge. In the present study, we investigate the effects of DJ NS1 Abs on mast cell-associated activities. We showed that administration of anti-DJ NS1 Abs into mice resulted in a reduction of mast cell degranulation and macrophage infiltration at local skin DENV infection sites. The production of DENV-induced chemokines (MCP-1, RANTES, and IP-10) and the percentages of tryptase-positive activated mast cells were also reduced by treatment with anti-DJ NS1 Abs. These results indicate that Abs against NS1 protein provide multiple therapeutic benefits, some of which involve modulating DENV-induced mast cell activation.Laboratory Investigation advance online publication, 27 February 2017; doi:10.1038/labinvest.2017.10.
 ...
PMID:Antibodies against nonstructural protein 1 protect mice from dengue virus-induced mast cell activation. 2824 Jul 47