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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin (ET) has been shown to contract both vascular and nonvascular smooth muscle and to stimulate human nasal glandular secretion of serous and mucous cell products. Some effects of ET are thought to be mediated by eicosanoid production. To explore the direct effect of ET on arachidonate metabolism in cultured human nasal mucosal explants, eicosanoids were measured after ET-1 stimulation. After labeling the explants with [3H]arachidonic acid (AA), supernatant from control and ET-1-treated explants were fractionated by reverse-phase high-performance liquid chromatography (HPLC). The resulting elution pattern suggested the release of prostaglandin (PG) E2 and AA in response to ET-1 stimulation. Radioimmunoassay after HPLC resolution confirmed that ET-1 induced a significantly increased release of PGE2 as well as PGD2, PGF2 alpha, thromboxane B2, and 15-hydroxyeicosatetraenoic acid (15-HETE). Although significant amounts of 15-HETE were generated, cyclooxygenase product generation was most remarkable. Eicosanoid release after ET-1 exposure (10 to 0.1 microM) is concentration dependent and occurs within 1 h. Whereas 15-HETE release was maximal at 4 h, prostanoid production was maximal 1 h after exposure to ET-1. Other assayed AA metabolites, including the peptidoleukotrienes, did not significantly change after ET-1 stimulation. We conclude that ET-1 induces the release of predominantly cyclooxygenase products from cultured human nasal mucosal explants.
Am J Respir Cell Mol Biol 1992 Feb
PMID:Endothelin-1 stimulates eicosanoid production in cultured human nasal mucosa. 131 93

Activated neutrophils produce a wide array of products (free radicals, arachidonate metabolites, degradative enzymes), cause hemodynamic effects and increased permeability in isolated blood-free perfused lungs, and evoke direct injury to cultured endothelial cells. The aims of this study were to investigate the response of isolated rat pulmonary arterial rings to activated neutrophils, the role of intact endothelium in these responses, and which neutrophil products were responsible for the observed effects. Neutrophils activated with phorbol myristate acetate caused an initial increase in tension and a subsequent decreased recovery contraction to KCl. Neutrophils activated with formylmethionylleucylphenylalanine also caused an increase in tension but did not result in decreased recovery, suggesting different mechanisms for these two effects. The contractile response was dependent on endothelium, whereas the decline in recovery still occurred in the absence of endothelium. Filtrate from activated neutrophils did not cause the contractile response, but recovery was decreased. Neither addition of catalase + superoxide dismutase nor decreased superoxide release due to prior activation of neutrophils altered the initial contraction or the decline in recovery contractile ability, suggesting that oxygen free radical products were not responsible for either effect. The cyclooxygenase inhibitors (ibuprofen and indomethacin), the thromboxane A2 synthetase inhibitor (OKY-046), and pretreatment of the neutrophils with aspirin inhibited the contractile response but did not prevent the decrease in recovery. A mixture of antiproteases did not protect the arterial muscle from the decline in recovery. Although cyclooxygenase products may be involved in initiating the contraction in response to activated neutrophils, the mechanism resulting in subsequent loss of force-developing ability is unclear.
Am J Respir Cell Mol Biol 1992 Mar
PMID:Activated neutrophils alter contractile properties of the pulmonary artery. 131 94

Modification of the silica surface has been shown to reduce its cytotoxicity in vitro and its fibrogenic activity in vivo. We have shown silica to be a potent stimulator of arachidonic acid (AA) metabolism in bovine alveolar macrophages (BAM). To determine the effect of surface-modified silica on AA metabolism in BAM, we exposed BAM in vitro to silica treated with aluminum lactate or polyvinylpyridine-N-oxide (PVPNO). BAM were prelabeled with [3H]AA and incubated with 3 and 5 mg of silica. Unmodified silica at these doses elicited maximal AA metabolite release from BAM. AA metabolites were analyzed by high performance liquid chromatography. Lactate dehydrogenase release was quantitated to determine the cytotoxicity of treated and untreated silica on BAM. Treating silica with aluminum lactate or PVPNO significantly (P less than or equal to 0.05) reduced 5-lipoxygenase metabolite release and significantly (P less than or equal to 0.05) increased cyclooxygenase metabolite release. These changes in AA metabolite release were accompanied by a significant (P less than or equal to 0.05) reduction in the cytotoxicities of the treated silicas compared with untreated silica. Our results suggest that the reduced inflammatory and fibrogenic activity of surface-modified silica may in part be due to reduced AA metabolite release from exposed macrophages.
Am J Respir Cell Mol Biol 1992 May
PMID:Diminished arachidonic acid metabolite release by bovine alveolar macrophages exposed to surface-modified silica. 131 33

Primary cultures of guinea pig tracheal epithelial cells maintained in an air/liquid interface system that maintains differentiated characteristics were grown to near confluence and exposed for 1 h to platelet-activating factor (PAF) on both apical and basal sides. PAF provoked release of high-molecular-weight mucin-like glycoproteins (MLG) from the cells, with maximal stimulation occurring at 10(-8) and 10(-9) M. The inactive form of PAF, lyso-PAF, was without effect. Indomethacin, the cyclooxygenase inhibitor, did not affect secretion stimulated by PAF, but nordihydroguiaretic acid (NDGA), a mixed cyclooxygenase and lipoxygenase inhibitor, attenuated secretion stimulated by PAF in a concentration-dependent manner. High performance liquid chromatography assay of the culture medium after addition of PAF revealed increased production of 15-, 12-, and 5-hydroxyeicosatetraenoic acids (15-, 12-, and 5-HETEs). The stimulatory effect of PAF on both mucin secretion and formation of HETEs was inhibited by the PAF receptor antagonists, CV-3988 and Ro 19 3704, with Ro 19 3704 acting at a concentration 10-fold lower than CV-3988 in inhibiting both effects. When added exogenously to the cell cultures, the combination of 5-, 12-, and 15-HETEs stimulated MLG release in a concentration-dependent manner. The results suggest that PAF stimulates release of MLG by guinea pig airway epithelium in vitro by a mechanism involving binding of PAF to receptors on epithelial cell surfaces, stimulation of lipoxygenase metabolism of arachidonic acid to HETEs within the epithelium, and stimulation of secretion by these epithelial-derived HETEs via an autocrine or paracrine mechanism.
Am J Respir Cell Mol Biol 1992 May
PMID:Platelet-activating factor provokes release of mucin-like glycoproteins from guinea pig respiratory epithelial cells via a lipoxygenase-dependent mechanism. 131 34

The aim of this study was to clarify whether or not arachidonic acid metabolic disorders are caused by a substrate inavailability and whether such disorders might contribute to circulatory disturbances in the diabetic myocardium. Norepinephrine induced a decrease in the conductivity of both coronary arterial bed and myocardial microcirculation in alloxan-diabetic dogs. It was markedly (p less than 0.05) attenuated both by indomethacin and acetylsalicylic acid pretreatments indicating an imbalance among the vasoactive prostanoids in diabetes. TXA2 release from the diabetic coronary rings was found to be elevated and could be normalized after the blockade of vascular adrenoceptors by phentolamine (p less than 0.05). PGI2 synthesis was also enhanced by adrenergic blockade in the diabetic arterial rings. After pretreatment with 14C arachidonic acid, in order to measure substrate availability, the arachidonic acid metabolic rate was less in the diabetic coronary arteries than in healty vessels (p less than 0.05). Ten mumol/l norepinephrine decreased arachidonic acid metabolism in the presence of prelabelled substrate in the diabetic animals, compared to an increase observed in metabolically healthy dogs. Therefore diabetes appears to diminish arachidonic acid metabolism and uptake independent of adrenoceptors and to induce an imbalance between vasoconstrictor and vasodilator cyclooxygenase products, resulting in elevated TXA2 release controlled by adrenergic mechanisms which may contribute to an impairment in myocardial microcirculation.
Mol Cell Biochem 1992 Feb 12
PMID:Disturbed lipid metabolism in diabetic coronary vessels. 132 Jul 34

Exposure of rats to ozone (O3) produces an increase in airway permeability and a concomitant influx of polymorphonuclear leukocytes in the lung. These observations raise the possibility that the inflammatory cells play a role in the cellular injury and increased airway permeability after O3 exposure. This study was therefore designed to determine if the inflammatory cells or their products are essential for the O3 effect. In a series of experiments, rats were rendered leukopenic with cyclophosphamide, treated with leukotriene B4 (LTB4), or with the inhibitors of lipoxygenase or cyclooxygenase products of arachidonic acid, followed by exposure to O3. A 2-h exposure to 0.8 ppm O3 caused a significant increase in the flux of proteins and albumin in bronchoalveolar lavage (BAL) and elevated the transport of 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA) from trachea to blood. The treatment with cyclophosphamide caused a significant reduction in the circulating and pulmonary leukocytes and prevented an increase in tracheal mucosal permeability to 99mTc-DTPA and the protein and albumin flux in BAL. While the intratracheal instillation of LTB4 did not affect the permeability, tracheal permeability and albumin levels in BAL in rats treated with LTD4 antagonist FPL 55712 and exposed to O3 were lower than in the untreated O3-exposed rats. Pretreatment with indomethacin also prevented the O3 effects, as reflected by the decreased protein and albumin flux in BAL and 99mTc-DTPA transport from trachea to blood. These data show a reduction in the effect of O3 by agents that affect leukocytes or their products. The results support a mechanism of increased permeability that is dependent upon inflammatory cells and their products.
Am J Respir Cell Mol Biol 1992 Jul
PMID:Attenuation of ozone-induced airway permeability in rats by pretreatment with cyclophosphamide, FPL 55712, and indomethacin. 132 Sep 4

Primary cultures of peripheral lung lobes were grown in a highly supplemented medium. Human lung endothelial cells (HLE) were isolated from the mixed population by FACS. The cells proliferated rapidly and were serially cultivated for at least 16 passages. Both early and late passage cells were positive for the standard endothelial markers. Factor VIII related-antigen (Factor VIII R-Ag), angiotensin-converting enzyme, acetylated low-density lipoprotein labeled with 1,1'-dioctadecyl-1,3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-Ac-LDL) uptake, and bound the lectin Ulex europaeus agglutinin (UEA). Prostaglandin E2 was the major cyclooxygenase product of HLE, in contrast to human umbilical vein endothelial cells (HUVE), which synthesized PGI2 in excess of PGE2. Factor VIII R-Ag exhibited a diffuse cytoplasmic as well as an extracellular fibrillar distribution in HLE, in contrast to a vesicular (Weibel-Palade body) cytoplasmic distribution in HUVE. The HUVE did demonstrate some extracellular fibrillar Factor VIII R-Ag as well. Urokinase was the predominant plasminogen activator (PA) secreted by HLE, whereas tissue PA was predominant in HUVE cultures. HLE formed tube-like structures within 2 h of plating on a Matrigel matrix whereas HUVE formed larger tube-like structures only after 1 or more days. The properties described here indicate that human lung microvessel endothelium can be isolated and continuously grown from small tissue segments and express a number of properties that differ from those of HUVE. These studies provide further support for the concept that endothelial cells from different sources can exhibit considerable heterogeneity relating to their phenotypic and biochemical properties.
Am J Respir Cell Mol Biol 1992 Dec
PMID:Isolation, cultivation, and partial characterization of microvascular endothelium derived from human lung. 133 46

Five homogenates of human sperm cells were separately incubated with [14C]arachidonic acid in the presence of reduced glutathione, L-tryptophan, and haematin as cofactors. The cyclooxygenase products of arachidonic acid metabolism were extracted, separated, and measured for their radioactivity. The rate of formation of prostaglandin (PG)D2, PGE2, PGF2 alpha, 6-keto PGF1 alpha, and thromboxane (TX)B2 were 18.0 +/- 1.11, 10.9 +/- 0.68, 5.8 +/- 0.21, 3.9 +/- 0.13 and 6.6 +/- 0.52 pmol/10(6) cells/min, respectively. These results are discussed in relation to the hypothesis that cyclooxygenase metabolites of certain polyunsaturated fatty acids play an important part in the sperm acrosome reaction and fertilization.
Mol Reprod Dev 1992 Nov
PMID:Biosynthesis of prostaglandins by human spermatozoa in vitro and their role in acrosome reaction and fertilization. 144 96

The condensed tannin present in cotton mill dust profoundly alters the functional capabilities of resident alveolar macrophages. Previous studies from this laboratory have shown that in vitro exposure of rabbit resident alveolar macrophages to condensed tannin significantly inhibits the ability of these cells to produce reactive oxygen intermediates or to ingest particles. In the present study, we demonstrate that condensed tannin also alters arachidonic acid (C20:4) metabolism in these cells. Exposure of rabbit resident alveolar macrophages to condensed tannin results in the time- and dose-dependent release of C20:4 from the membrane phospholipids. The release of C20:4 occurred only at tannin concentrations greater than 25 micrograms/ml and was maximal 90 min after the onset of exposure. The EC50 for release was 75 micrograms/ml. Exposure to 100 micrograms/ml tannin resulted in the release of 20 +/- 3% of the [14C]C20:4 incorporated in the cell membrane. In comparison, exposure to 160 micrograms/ml zymosan resulted in the release of 14 +/- 4% of the [14C]C20:4. For both tannin and zymosan, phosphatidylcholine and phosphatidylinositol were the principal sources of the released C20:4. Approximately 63% of the C20:4 released after zymosan stimulation was further metabolized, mainly via the cyclooxygenase pathway. The major metabolites were 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, and prostaglandin E2. In contrast, only 24% of the C20:4 released by tannin was subsequently further metabolized. The metabolites formed were essentially evenly distributed between products of the cyclooxygenase pathway and the lipoxygenase pathway. Exposure of alveolar macrophages to 50 micrograms/ml tannin for 30 min reduced the ability of the cells to subsequently incorporate C20:4 by 50 to 70%. In contrast, exposure of the cells to 160 mg/ml zymosan for 30 min had only a minimal effect on the subsequent ability of these cells to incorporate C20:4. These results indicate that tannin promotes C20:4 release, at least in part, by inhibiting its reacylation back into phospholipids, a mechanism that differs from that of zymosan.
Am J Respir Cell Mol Biol 1992 Aug
PMID:Condensed tannin promotes the release of arachidonic acid from rabbit resident alveolar macrophages. 149 6

Our object was to obtain information about the regulatory mechanism which modulates the effect of basic fibroblast growth factor (bFGF) on commitment to growth in human umbilical vein endothelial (HUVE) cells. Firstly, phorbol ester PMA, a known activator of protein kinase C (PKC), was found to be able to act synergistically with bFGF to stimulate 3H thymidine incorporation in HUVE cells. Secondly, bFGF and PMA induced a stimulated phospholipase A2 (PLA2)-catalyzed release of 14C arachidonate. Thirdly, inhibitors of PLA2, PKC and HETE, but not an inhibitor of cyclooxygenase metabolites, inhibited FGF/PMA-stimulated DNA synthesis. Fourth, the stable cyclooxygenase metabolite of prostacyclin was not found to be changed when cells were treated with bFGF plus PMA. The present data suggest that PKC is able of acting synergistically with bFGF in order to stimulate DNA-primary initiation activity in HUVE cells via the PLA2-dependent generation of lipoxygenase metabolites such as HETE.
Cell Mol Biol 1992 Jul
PMID:Possible involvement of arachidonic acid metabolites in the synergistic action of endothelial mitogenesis by basic fibroblast growth factor and phorbol ester. 149 42


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