Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nedocromil sodium (10(-10) - 10(-9) M) produced a dose-related inhibition of superoxide anion generation induced by platelet activating factor (PAF) in human polymorphonuclear leukocytes (PMNs). At a higher concentration (3 x 10(-7) M), nedocromil sodium significantly inhibited superoxide generation elicited by N-formyl-methionyl-leucylphenylalanine, but was unable to block the response to phorbol dibutyrate. Nedocromil sodium (10(-11) - 10(-5) M) enhanced PAF-stimulated lysozyme release in a non-concentration-dependent manner, and was completely ineffective in depressing PAF-induced release of [3H]arachidonic acid and the rise in cytosolic Ca2+. The preferential inhibitory effects of nedocromil sodium on PAF-induced activation of superoxide generation may provide insight into the therapeutic action of this drug as an anti-asthmatic agent.
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PMID:Differential inhibition by nedocromil sodium of superoxide generation elicited by platelet activating factor in human neutrophils. 196 61

Nedocromil sodium and cromolyn (sodium cromoglycate) are prophylactic agents in asthma which were initially found to be inhibitors of mast cell activation. Recent evidence has suggested that their effects on granulocyte-mediated reactions may contribute to their therapeutic effects. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF) enhance the activity of granulocytes in antibody-dependent cell-mediated cytotoxicity (ADCC). Preincubation of purified neutrophils or eosinophils with nedocromil sodium or cromolyn partially inhibited their ability to mediate ADCC when stimulated by GM-CSF or TNF. Preincubation with nedocromil sodium did not alter the ability of neutrophils to produce superoxide or release lysozyme in response to soluble or phagocytic stimuli, and GM-CSF-enhanced superoxide production triggered by chemotactic peptide was not altered in such drug-treated neutrophils. After nedocromil sodium treatment, neutrophils showed no consistent changes in TNF-stimulated adherence to either plastic culture wells or umbilical vein endothelium. These findings demonstrate that nedocromil sodium and cromolyn directly and selectively affect the function of granulocytes in vitro. While drug-treated granulocytes were impaired in immune-directed cytotoxicity stimulated by GM-CSF or TNF, activation of other granulocyte functions by the same stimuli was intact.
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PMID:Nedocromil sodium and cromolyn (sodium cromoglycate) selectively inhibit antibody-dependent granulocyte-mediated cytotoxicity. 284 86

Both PAF (10 microM) and bradykinin (0.1-10 microM) increased lysozyme (from submucosal gland serous cells (+138 and +45% for PAF, 10 microM, and bradykinin, 1 microM, respectively) and albumin (mainly active epithelial transport; +387 and +108%) outputs into the ferret tracheal lumen in vitro and reduced the negativity of the potential difference (PD: -33 and -17%) across the trachea. Since PAF can cause bronchial smooth muscle hyperresponsiveness, we tested whether these effects were interactive, and if PAF would increase the actions of bradykinin. The bradykinin-induced lysozyme and albumin outputs were more than trebled and the PD change was enhanced by PAF, after the immediate secretory effects of the latter had returned to baseline. The secretory and PD responses to PAF were all prevented by the PAF-antagonist WEB 2086 and by a combination of the free-radical scavengers catalase and SOD, indicating that PAF may act on specific receptors to release free-radicals. Nedocromil sodium inhibited the increase in lysozyme and albumin outputs produced by PAF, but had no effect on the PD response. None of the tracheal responses to bradykinin was modified by WEB 2086, catalase and SOD, or nedocromil sodium. The secretory and PD hyperresponsiveness to bradykinin caused by PAF was prevented by WEB 2086 and by catalase and SOD. Nedocromil sodium greatly inhibited the lysozyme and albumin hyperresponsiveness but had no effect on the PD response. Thus PAF may release more than one type of radical which have differential effects on serous cells and albumin transport compared with PD; nedocromil sodium may act only against the radical causing the secretory effects.
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PMID:PAF-induced secretory hyperresponsiveness in the ferret trachea to bradykinin and its pharmacological inhibition. 951 26