Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasculitis is commonly seen during systemic Haemophilus somnus infections. Although, the mechanism of vascular damage is not completely understood, in a previous report we demonstrated that H. somnus and its lipooligosaccharide (LOS) induced apoptosis in bovine pulmonary artery endothelial cells in vitro. In the present study, we investigated the role of caspase activation in LOS-mediated apoptosis of bovine endothelial cells. Exposure to H. somnus LOS induced caspase-3 activation and chromatin condensation in endothelial cells. These responses were blocked by the addition of a pan-caspase inhibitor (z-VAD-fmk) or capase-3 inhibitor (DEVD-fmk). Incubation of endothelial cells with H. somnus LOS also induced activation of the initiator caspases, caspases-8 and 9, with the activity of the former increasing more rapidly than the latter. Addition of a caspase-8 inhibitor (IETD-fmk) significantly reduced LOS-mediated apoptosis, whereas, addition of a caspase-9 inhibitor (LEHD-fmk) had little effect. These data suggest that LOS-mediated activation of caspase-3 and apoptosis of endothelial cells is caspase-8 dependent.
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PMID:Caspase activation during Haemophilus somnus lipooligosaccharide-mediated apoptosis of bovine endothelial cells. 1458 Mar 92

Activated phagocytes express considerable amounts of MRP8 and MRP14, 2 calcium-binding S100 proteins forming stable heterodimers that are specifically secreted at inflammatory sites in many diseases. We previously reported that treatment of human microvascular endothelial cells with purified MRP8/MRP14 leads to loss of endothelial cell contacts. In this study, we demonstrate that MRP8/MRP14 complexes furthermore trigger cell death of endothelial cells after the onset of cell detachment. Morphologic analysis of dying endothelial cells revealed characteristic features of both apoptosis and necrosis. Furthermore, MRP8/MRP14 induced apoptotic caspase-9 and caspase-3 activation, DNA fragmentation, and membrane phosphatidylserine exposure in target cells. These events were independent of death receptor signaling and in part controlled by a mitochondrial pathway. Consistently, overexpression of antiapoptotic Bcl-2 abrogated caspase activation and externalization of phosphatidylserine; however, MRP8/MRP14 still induced plasma membrane damage and even DNA fragmentation. Thus, our results demonstrate that MRP8/MRP14 triggers cell death via caspase-dependent as well as -independent mechanisms. Excessive release of cytotoxic MRP8/MRP14 by activated phagocytes might therefore present an important molecular pathomechanism contributing to endothelial damage during vasculitis and other inflammatory diseases.
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PMID:MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and -independent cell death program. 1709 18

A common feature of severe sepsis is vascular inflammation and damage to the endothelium. Because platelets can be directly activated by bacteria and endotoxin, these cells may play an important role in determining the outcome of sepsis. For example, inhibiting platelet interactions with the endothelium has been shown to attenuate endothelial cell damage and improve survival during sepsis. Although not entirely understood, the interactions between bacteria-activated platelets and the endothelium may play a key role in the vascular pathology of bacterial sepsis. Haemophilus somnus is a bacterial pathogen that causes diffuse vascular inflammation and endothelial damage. In some cases H. somnus infection results in an acute and fatal form of vasculitis in the cerebral microvasculature known as thrombotic meningoencephalitis (TME). In this study, we have characterized the mechanisms involved in endothelial cell apoptosis induced by activated platelets. We observed that direct contact between H. somnus-activated platelets and endothelial cells induced significant levels of apoptosis; however, Fas receptor activation on bovine endothelial cells was not able to induce apoptosis unless protein synthesis was disrupted. Endothelial cell apoptosis by H. somnus-activated platelets required activation of both caspase-8 and caspase-9, as inhibitors of either caspase inhibited apoptosis. Furthermore, activated platelets induced endothelial cell production of reactive oxygen species (ROS) and disrupting ROS activity in endothelial cells significantly inhibited apoptosis. These findings suggest that bacterial activation of platelets may contribute to endothelial cell dysfunction observed during sepsis, specifically by inducing endothelial cell apoptosis.
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PMID:Endothelial cell apoptosis induced by bacteria-activated platelets requires caspase-8 and -9 and generation of reactive oxygen species. 1827 69