Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An anaphylactic mechanism involving IgE-sensitized basophils is necessary for immune complex deposition in rabbits. Basophils under stimulation by the IgE-bound antigen actively release a platelet-activating factor. Increased vascular permeability results from action of vasoactive amines from basophils and from aggregated platelets and possibly direct action of PAF on vascular walls. This allows trapping of circulating complexes along vascular membranes. Once deposited complexes produce tissue injury by neutrophil-complement-dependent mechanisms. However, complex deposition seems pathogenic in itself for the glomerular basement membrane. PAF is a 1,100-dalton MW lipid, with hydrophobic properties and positive charge; it exists in human basophils. Patients suffering from SLE or undergoing anaphylactic shocks exhibit marked reduction of basophil counts and PAF level. We propose that anaphylactic increase of vasopermeability may be a common feature at early stages of many immune diseases associated with severe structural injury.
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PMID:Passage of immune complexes through vascular walls. Evidence for the role of an immediate hypersensitivity mechanism and its mediator: platelet-activating factor. 5 75

The biologically active 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet-activating factor; PAF) is inactivated in plasma mainly by a specific PAF acetylhydrolase (1-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine acetylhydrolase; EC 3.1.1.48). In the present study, PAF was released in detectable amounts (5.4 +/- 2.9 ng/ml; mean +/- 1 SD) in the plasma of 8 out of 10 patients with systemic lupus erythematosus (SLE) during the most active phases of the disease. PAF was never detectable in the plasma of patients with inactive SLE or of healthy subjects. PAF acetylhydrolase activity was markedly reduced in sera of 10 patients with active SLE as compared to 7 patients with inactive SLE, 16 patients with rheumatoid arthritis (RA), 5 patients with nephrotic syndrome (NS) and 15 healthy subjects. A kinetic study of the enzyme in patients with active SLE suggested an overall reduced activity rather than an intrinsic defect of the enzyme. PAF acetylhydrolase in sera of patients with active SLE shared with that of healthy subjects the same substrate specificity, sensitivity to enzymatic and chemicophysical treatments and association to low-density lipoprotein (LDL), acting as carrier of PAF acetylhydrolase in plasma. However, the protein concentration of LDL was significantly reduced in patients with active SLE as compared to patients with inactive SLE, RA and NS and to healthy subjects, thereby suggesting that the reduction of PAF acetylhydrolase activity in active SLE might be due at least in part to a carrier defect related to the activity of the disease. In addition, experiments in which serum of patients with active SLE and serum of healthy subjects were mixed in different combinations indicated the absence of factors inhibiting PAF acetylhydrolase activity in SLE patients.
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PMID:Release of platelet-activating factor in systemic lupus erythematosus. 235 68

A 37-year-old female who suffered from SLE had a bleeding disorder. At the time of initial evaluation, the main disease demonstrated was a delta-storage pool deficiency. After this improved, a marked decrease of aggregation still remained, when induced by either ADP, epinephrine, collagen, A23187, thrombin, or PAF-acether. Although arachidonate-induced aggregation was slightly decreased, thromboxane B2 was produced normally in response to exogenous arachidonate. The patient's endoperoxides and/or thromboxane A2 aggregated aspirin-treated platelets, though her platelets were themselves unresponsive. Impaired aggregability induced by TPA (12-0-tetradecanoylphorbol-13-acetate) or OAG (1-oleoyl-2-acetyl-glycerol) was also found. However, the phosphorylation of P43 and P20 induced by several stimulators including CA++ ionophore was normal, using 32P-labelled platelets. It is suggested that TPA or OAG-induced platelet aggregation requires not only the phosphorylation of those proteins, but also another unknown mechanism after the phosphorylation, and that the platelet dysfunction of this patient was due to a defect of some mechanism involving Ca++ uptake or mobilization of cytoplasmic Ca++ from intracellular storage sites.
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PMID:A defect of platelet release reaction in a patient with SLE: impaired platelet aggregation induced by phorbol ester with a normal phosphorylation of 40K protein. 308 95

Urine from normotensive volunteers and patients with systemic lupus erythematosus glomerulonephropathy was sequentially concentrated by negative-pressure ultrafiltration, dialyzed against distilled water, and extracted into the chloroform phase of a mixture of organic solvents(chloroform:methanol:water, 1:1:0.9 vol/vol). The lipid fraction was further purified by thin-layer chromatography on silica gel plates using neutral, acidic, and basic mixtures of organic solvents and it was then tested for its ability to induce the release of [3H]serotonin from rabbit platelets. All of the samples contained a platelet-activating moiety similar to a synthetic platelet-activating factor (PAF-acether) on the basis of its chromatographic behavior, resistance to the pretreatment of platelets by 10(-6) M indomethacin, and loss of activity by alkaline methanolysis or treatment by phospholipases A2, C, and D. Cross-densensitization experiments between synthetic PAF-acether and the urine factor showed that both compounds act on platelets through the activation of the same putative receptor. Further, the urine factor induced hypotension when intra-arterially injected in normotensive rats, and this activity was also abrogated by alkaline methanolysis. In summary, these data provide evidence of the presence in normal human urine and, probably, of the release by the kidney of a lipid factor with platelet-activating and hypotensive activity whose general structure seems to be alkyl-acyl-glyceryl-phosphorylcholine and, therefore, is similar to the structure of the inflammatory mediator PAF-acether and the antihypertensive polar renomedullary lipid.
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PMID:Presence in normal human urine of a hypotensive and platelet-activating phospholipid. 685 62

Basophil degranulation and release of platelet-activating factor (PAF acether) have been implicated in enhanced vascular permeability and immune complex deposition in rabbit acute serum sickness. PAF-acether is a phospholipid mediator of anaphylaxis, released from leukocytes of several mammalian species, including man, that aggregates platelets and releases their vasoactive amines. In this article, we evaluated the occurrence of basophil degranulation and release of PAF-acether in patients with systemic lupus erythematosus. In the acute phases of the disease, basophils were in vivo degranulated, and the amount of PAF-acether releasable from leukocytes was markedly reduced. During remission or in the latent phases of the disease, when the number of metachromatically staining basophils increased. in an vitro degranulation and release of PAF-acether were observed after DNA challenge. Electron microscopy studies demonstrated that basophils indeed degranulated in response to DNA. These studies also showed the interaction between degranulating basophils and human platelets which aggregated even if the other two pathways of human platelet aggregation, i.e., the ADP- and the arachidonic acid-dependent pathways, were blocked. The concomitance of basophil degranulation and release of PAF-acether, together with the morphologic evidence of the interaction between degranulating basophils and aggregated platelets, was strongly suggestive of release of PAF-acether from basophils in systemic lupus erythematosus.
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PMID:Release of platelet-activating factor in human pathology. I. Evidence for the occurrence of basophil degranulation and release of platelet-activating factor in systemic lupus erythematosus. 746 48

To establish a metabonomic method based on high performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-Q-TOF/MS), in order to study the changes in serum metabolites of systemic lupus erythematosus (SLE) mice after treatment of Jieduquyuziyin prescription, the pathogenesis of SLE and mechanism of drug action. The orthogonal partial least squares (OPLS) was applied for the pattern recognition of experimental data, finding a significant difference in the control group, the SLE model group, the Jieduquyuziyin prescription-treated group and the prednisone acetate-treated group. According to the OPLS load diagram, 12 differential metabolites, including traumatic acid, PAF, 12 (S)-HEPE, 15(S)-HETrE and Hepoxilin B3 were identified by using accurate mass combined with MS/MS data After treatment with Jieduquyuziyin prescription, the relative contents of PAF, 12 (S)-HETE were close to the level of the control group. According to the analysis on metabolic pathway, SLE could cause significant changes in unsaturated fatty acid and amino acid metabolism pathway, while Jieduquyuziyin prescription has a effect in regulating disorder of unsaturated fatty acid metabolism pathway.
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PMID:[Study on intervention effect of Jieduquyuziyin prescription systemic lupus erythematosus by HPLC-Q-TOF/MS]. 2449 66