Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aortic elastase and neutrophil elastase is higher in patients with abdominal aortic aneurysms. The purpose of this study was to determine if these proteolytic elevations occur after abdominal aortic aneurysms have been repaired. Specifically, we studied the stimulation and inhibition of elastase degranulation from neutrophils in postoperative abdominal aortic aneurysm patients compared to aortic occlusive disease patients. Neutrophil elastase was determined in postoperative abdominal aortic aneurysm and aortic occlusive disease patients in response to calcium and the ionophore A23187. Inhibition of elastase release was determined with the calcium channel blocking agent Verapamil. Neutrophil elastase secretion was significantly higher in the abdominal aortic aneurysm patients (47%) versus aortic occlusive disease (20%) (p less than .05), while the effect of Verapamil in blocking this response was significantly lower in the abdominal aortic aneurysm patients (14%) compared to aortic occlusive disease patients (27%) (p less than .02). The time for degranulation to occur was longer in the abdominal aortic aneurysm patients (14.7 minutes) versus aortic occlusive disease patients (3.5 minutes), but the rate of secretion was not different between the two groups. These data indicate that, (1) neutrophils secrete more elastase in response to a calcium stimulus in abdominal aortic aneurysm patients; (2) it takes longer to secrete the increased amount of elastase in abdominal aortic aneurysm patients since the rate of secretion is similar between the two groups; and (3) Verapamil blocks elastase secretion ineffectively in abdominal aortic aneurysm patients. We conclude that the proteolytic alterations in abdominal aortic aneurysm patients are more likely a primary event and not a response to the abdominal aortic aneurysm and that Verapamil is a poor drug to use to medically manipulate the protease system in abdominal aortic aneurysm patients.
 ...
PMID:The calcium messenger system and the kinetics of elastase release from human neutrophils in patients with abdominal aortic aneurysms. 217 37

The neutral proteinase elastase is released from polymorphonuclear (PMN) leukocytes in various physiological and pathological conditions. Aim of the present study was to gain further insight into the mechanisms which govern the liberation of this proteinase. Therefore, the effects of the calcium ionophore A23187 and of the protein kinase C activator phorbol myristate acetate (PMA) on neutrophils were investigated in human whole-blood samples. Furthermore, the inhibitory effects of the calcium channel blocker verapamil and of the calmodulin blocker trifluoperazine were followed. A23187 induced a release of elastase from neutrophils in a dose- and time-dependent manner. Complexation of extracellular calcium by ethylenediamine tetraacetate (EDTA) completely abolished the stimulatory effect of A23187. In a concentration of 10(-4) M verapamil was capable of attenuating (-49%) the A23187-induced secretion of PMN elastase. Besides the increase in intracellular calcium concentration, the activation of protein kinase C by PMA did also cause a release of neutrophil elastase. This release was strictly depending on the concentration of PMA and the time of incubation. In contrast to the stimulatory effect of A23187, the PMA-induced liberation of neutrophil elastase was attenuated, but not completely abolished, by complexation of extracellular calcium with EDTA. Both 10(-4) M verapamil (-43%) and 10(-5) M trifluoperazine (-42%) were able to reduce the PMA-induced release of neutrophil elastase. Based upon these data, we conclude that both the translocation of calcium intracellularly by A23187 and the activation of protein kinase C by PMA stimulate the release of neutrophil elastase. Verapamil and trifluoperazine were capable of suppressing the stimulation of elastase release.
 ...
PMID:Stimulation and inhibition of elastase release from human neutrophil-dependence on the calcium messenger system. 311 99

The neutral proteinase elastase is released from polymorphonuclear (PMN) leukocytes in various physiological and pathological conditions. Aim of the present study was to gain further insight into the mechanisms which govern the liberation of this proteinase. Therefore, the effects of the calcium ionophore A23187 and of the protein kinase-C activator phorbol myristate acetate (PMA) on neutrophils were investigated in human whole-blood samples. Furthermore, the inhibitory effects of the calcium channel blocker verapamil and of the calmodulin blocker trifluoperazine were followed. A23187 induced a release of elastase from neutrophils in a dose- and time-dependent manner. Complexation of extracellular calcium by ethylenediamine tetraacetate (EDTA) completely abolished the stimulatory effect of A23187. In a concentration of 10(-4) M verapamil was capable to attenuate (-49%) the A23187-induced secretion of PMN elastase. Beside the increase in intracellular calcium concentration, the activation of protein kinase C by PMA did also cause a release of neutrophil elastase. This release was strictly depending on the concentration of PMA and the time of incubation. In contrast to the stimulatory effect of A23187, the PMA-induced liberation of neutrophil elastase was attenuated, but not completely abolished, by complexation of extracellular calcium with EDTA. Both 10(-4) M verapamil (-43%) and 10(-5) M trifluoperazine (-42%) were able to reduce the PMA-induced release of neutrophil elastase. Based upon these data, we conclude that both the translocation of calcium intracellularly by A23187 and the activation of protein kinase C by PMA stimulate the release of neutrophil elastase. Verapamil and trifluoperazine were capable to suppress the stimulation of elastase release.
 ...
PMID:Stimulation and inhibition of elastase release from human neutrophils dependent on the calcium messenger system. 312 93

Activated neutrophils are assumed to be one plausible cause of tissue injury in the ischaemic and reperfused myocardium. We studied the inhibitory effects of the calcium antagonists felodipine, nimodipine and verapamil on human neutrophil activation in order to elucidate the mechanisms underlying their myocardioprotective effects and to determine whether calcium antagonists with different chemical structures vary in their effect on neutrophil activation. Neutrophils were stimulated with formyl-Met-Leu-Phe (0.1 microM) or by phorbol myristate acetate (0.16 microM), and the rise in cytosolic calcium and the H2O2 production were determined. For felodipine, the inhibitory effect on granulocyte elastase release was also studied. The calcium antagonists reduced formyl-Met-Leu-Phe and phorbol myristate acetate-induced neutrophil activation in a concentration-dependent manner, the order of potency being: felodipine > nimodipine > verapamil. For felodipine, the IC50 (concentration causing 50% reduction) values were 3 x 10(-6) and 2 x 10(-6) M for the formyl-Met-Leu-Phe-induced cytosolic calcium increase and H2O2 production, respectively. The IC50-value for the phorbol myristate acetate-induced cytosolic calcium increase was 6 x 10(-6) and for H2O2 production 4 x 10(-6) M. For formyl-Met-Leu-Phe-induced granulocyte elastase release, the IC50-value was 5 x 10(-6) M. The inhibitory effect of felodipine on the phorbol myristate acetate-induced granulocyte elastase release did not exceed 50%. Nimodipine was a less potent inhibitor than felodipine for both formyl-Met-Leu-Phe- and phorbol myristate acetate-induced cell activities. Verapamil was even less potent than the other two agents. The present study demonstrates that felodipine potentially suppresses neutrophil activation at micromolar concentrations. However, this observation should not be directly extrapolated to explain the tissue protection by the compounds without evidence of profound local accumulation.
 ...
PMID:Effects of calcium blockers on the cytosolic calcium, H2O2 production and elastase release in human neutrophils. 900 Feb 58