Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral malaria is a severe form of the disease that may result, in part, from an overt inflammatory response during infection by Plasmodium falciparum. The understanding of the pathogenesis of cerebral malaria may aid in the development of better therapeutic strategies for patients. The immune response in cerebral malaria involves elevation of circulating levels of cytokines and chemokines associated with leukocyte accumulation and breakdown of the blood-brain barrier in the central nervous system. Platelet-activating factor (PAF) is a mediator of inflammation shown to orchestrate inflammatory processes, including recruitment of leukocytes and increase of vascular permeability. Using mice lacking the PAF receptor (PAFR(-/-)), we investigated the relevance of this molecule for the outcome and the neuroinflammatory process triggered by P. berghei ANKA, an experimental model of cerebral malaria. In PAFR(-/-) mice, lethality was markedly delayed and brain inflammation was significantly reduced, as demonstrated by histology, accumulation, and activation of CD8(+) T cells, changes in vascular permeability and activation of caspase-3 on endothelial cells and leukocytes. Similarly, treatment with the PAFR antagonist UK-74,505 delayed lethality. Taken together, the results suggest that PAFR signaling is crucial for the development of experimental cerebral malaria. Mechanistically, PAFR activation is crucial for the cascade of events leading to changes in vascular permeability, accumulation, and activation of CD8(+) T cells and apoptosis of leukocytes and endothelial cells.
 ...
PMID:Platelet-activating factor receptor is essential for the development of experimental cerebral malaria. 2207 30

Malaria-associated lung pathology has been a neglected area in the study of malaria complications. Platelet-activating factor (PAF) is an inflammatory mediator involved in lung inflammation. Using mice lacking the PAF receptor (PAFR(-/-)) we investigated the relevance of signaling through the PAFR for the lung inflammatory process triggered by Plasmodium berghei ANKA (PbA) strain infection. In PAFR(-/-) mice, pulmonary inflammation was markedly reduced as demonstrated by histology, production of certain pro-inflammatory mediators, accumulation of macrophage and CD8+ T cells in the lung parenchyma and the virtual absence of changes in vascular permeability. Therefore, PAFR activation is crucial in the pathogenesis of pulmonary damage associated with PbA infection in C57Bl/6 mice.
 ...
PMID:The role of platelet-activating factor receptor (PAFR) in lung pathology during experimental malaria. 2326 Jul 71