Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we investigated how chrysotile-stimulated macrophages generate superoxide using murine peritoneal macrophages, with special attention to the modulatory role of phospholipase A(2) (PLA(2)). We examined the effects of the following inhibitors and antagonists for signaling molecules on the superoxide anion (O(2)(-)) production of chrysotile-stimulated macrophages: p-bromophenacyl bromide (pBPB) and mepacrine for PLA(2); islet-activating protein (IAP) for G-protein; H-7 for protein kinase C (PKC); AA861 for 5-lipoxygenase (5-LO); indomethacin for cyclo-oxygenase (COX); ETYA for both 5-LO and COX; hexanolamine PAF for platelet-activating factor (PAF). The PLA(2) and PKC inhibitors effectively inhibited the chrysotile-induced superoxide anion production of macrophages, but not the G-protein inhibitor, the 5-LO and COX inhibitors, and the PAF antagonist. We also examined the effects of the PLA(2) inhibitors on macrophages stimulated by phorbol 12-myristate 13-acetate (PMA) which directly activates PKC. The two structurally different PLA(2) inhibitors showed differential effects on the PMA-induced superoxide generation: pBPB inhibited it but mepacrine did not. These results suggested that (1) PLA(2) and PKC modulate the chrysotile-induced O(2) production, and (2) two different kinds of PLA(2) work upstream and downstream of PKC, but (3) G-protein, 5-LO and COX metabolites, and PAF have no modulatory role in the reaction.
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PMID:Phospholipase A2-mediated superoxide production of murine peritoneal macrophages induced by chrysotile stimulation. 1085 8

The ability of Bothrops lanceolatus venom to induce neutrophil migration into the peritoneal cavity of mice was investigated. Intraperitoneal injection of venom caused dose- and time-dependent neutrophil migration, which peaked with 750 ng of venom/cavity 4h after venom injection. The neutrophil migration was significantly reduced by pretreatment with dexamethasone (0.5 mg/kg, s.c.), an indirect inhibitor of phospholipase A(2) (PLA(2)), and AA861 (0.01 mg/kg, s.c.), a 5-lipoxygenase inhibitor, but in contrast, was not modified by pretreatment with indomethacin (2 mg/kg, s.c.), an inhibitor of the cyclooxygenase pathway, meloxicam (5 mg/kg, s.c.), an inhibitor of the cyclooxygenase-2 pathway, or the PAF inhibitor WEB2086 (40 mg/kg, s.c.). Dexamethasone and AA861 also inhibited the neutrophil migration by 60% when administered immediately after venom injection, and the coadministration of these two drugs caused a 75% reduction in migration. BLV-induced neutrophil migration was not due to contamination by endotoxin since polymyxin B-treated venom retained its activity. Heating the venom (97 degrees C, 2 min) reduced the PLA(2) activity by 64% and this was accompanied by a corresponding reduction (68%) in neutrophil migration. These results suggest that arachidonate-derived lipoxygenase metabolites (possibly leukotriene B(4)) are involved in the chemotaxis observed. Macrophages may be an important source of these metabolites since the migratory response to venom was potentiated in mice pretreated with thioglycollate, but reduced when the peritoneal cavity was washed with sterile saline.
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PMID:Bothrops lanceolatus (Fer de lance) venom stimulates leukocyte migration into the peritoneal cavity of mice. 1246 67

Inhibition of phospholipase A(2) (PLA(2)) has recently been found to attenuate the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis (MS). However, the protective mechanisms that underlie PLA(2) inhibition are still not well understood. In this study, we found that cytosolic PLA(2) (cPLA(2)) was highly expressed in infiltrating lymphocytes and macrophages/microglia in mouse spinal cord white matter. Although cPLA(2) is also expressed in spinal cord neurons and oligodendrocytes, there were no differences observed in these cell types between EAE and control animals. Arachidonyl trifluoromethyl ketone (AACOCF3), a cPLA(2) inhibitor, significantly reduced the clinical symptoms and inhibited the body weight loss typically found in EAE mice. AACOCF3 also attenuated the loss of mature, myelin producing, oligodendrocytes, and axonal damage in the spinal cord white matter. Nitrotyrosine immunoreactivity, an indicator of peroxynitrite formation, was dramatically increased in EAE mice and attenuated by treatment with AACOCF3. These protective effects were not evident when AA861, an inhibitor of lipoxygenase, was used. In primary cultures of microglia, lipopolysaccharide (LPS) induced an upregulation of cPLA(2), inducible nitric oxide synthase (iNOS) and components of the NADPH oxidase complex, p47phox and p67phox. AACOCF3 significantly attenuated iNOS induction, nitric oxide production and the generation of reactive oxygen species in reactive microglia. Similar to the decomposition catalyst of peroxynitrite, AACOCF3 also blocked oligodendrocyte toxicity induced by reactive microglia. These results suggest that AACOCF3 may prevent oligodendrocyte loss in EAE by attenuating peroxynitrite formation in the spinal cord white matter.
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PMID:Arachidonyl trifluoromethyl ketone ameliorates experimental autoimmune encephalomyelitis via blocking peroxynitrite formation in mouse spinal cord white matter. 2168 98