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Results for “Group II Phospholipases A2”

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At least 19 recordsLinked to original sources

PubMed1992

Postoperative elevations of serum interleukin 6 and group II phospholipase A2: group II phospholipase A2 in serum is an acute phase reactant.

Elevations of serum immunoreactive interleukin 6 (IL-6) and Group II phospholipase A2 (M-PLA2) were observed without exception after elective surgeries for various sites. Serum IL-6 rose steeply after surgery, and reached the maximum level on the 1st postoperative day. Serum M-PLA2 increased from the 1st postoperative day and reached the maximum level on the 2nd postoperative day in 10 patients (76.9%), on the first day after surgery in 2 patients and on the 3rd day in one patient. The peak serum M-PLA2 after surgery was significantly correlated with the peak IL-6 and blood loss volume during surgery. These results suggested that serum M-PLA2 is an acute phase reactant.

Aged↗

PubMed1994

Pancreatic-type phospholipase A2 induces group II phospholipase A2 expression and prostaglandin biosynthesis in rat mesangial cells.

The effect of pancreatic group I phospholipase A2 (PLA2-I) on receptor-mediated expression of arthritic group II phospholipase A2 (PLA2-II) and its correlation with prostaglandin E2 (PGE2) synthesis were examined in cultured rat mesangial cells. Scatchard analysis using 125I-PLA2-I revealed the existence of a single class of specific binding sites for PLA2-I in rat mesangial cells with an equilibrium dissociation constant (Kd) of 1.6 nM and a maximum binding capacity of 10.1 fmol/10(6) cells. The mammalian mature type of PLA2-I specifically recognized this binding site, whereas its inactive zymogen and mammalian PLA2-II showed much lower affinities. PLA2-I markedly increased PLA2-II mRNA levels as well as PLA2-II secretion from the cells in a time- and dose-dependent manner that was closely correlated with PGE2 production. Both PLA2-II expression and PGE2 synthesis were completely suppressed by pretreatment of the cells with actinomycin D, cycloheximide, or dexamethasone. These results strongly suggest that there may be crosstalk between PLA2-I and PLA2-II via the specific PLA2-I receptor that elicits PGE2 synthesis.

Animals↗

PubMed1999

Protection by group II phospholipase A2 against Staphylococcus aureus.

Group II phospholipase A2 (PLA2) is an enzyme that has marked antibacterial properties in vitro. To define the role of group II PLA2 in the defense against Staphylococcus aureus, we studied host responses in transgenic mice expressing human group II PLA2 and group II PLA2-deficient C57BL/6J mice in experimental S. aureus infection. After the administration of S. aureus, the transgenic mice showed increased expression of group II PLA2 mRNA in the liver and increased concentration of group II PLA2 in serum, whereas the PLA2-deficient mice completely lacked the PLA2 response. Expression of human group II PLA2 resulted in reduced mortality and improved the resistance of the mice by killing the bacteria as indicated by low numbers of live bacteria in their tissues. Human group II PLA2 was responsible for the bactericidal activity of transgenic mouse serum. These results suggest a possible role for group II PLA2 in the innate immunity against S. aureus infection.

Animals↗

PubMed1997

Expression of human group II phospholipase A2 in transgenic mice.

Group II phospholipase A2 (PLA2) has been proposed to play an important role in inflammation and defense against bacterial infection. We investigated tissues of transgenic mice expressing the human group II PLA2 gene by immunohistochemistry using rabbit anti-human group II PLA2 antibodies, and by in situ hybridization by probing with human group II PLA2 mRNA anti-sense (test) and sense (control) riboprobes. By immunohistochemistry, human group II PLA2 was found in various mouse tissues and cell types including hepatocytes, proximal tubule cells of the kidney, epithelial cells of the renal pelvis, urinary bladder and ureter, granulosa cells of Graafian follicles, aortic intima and media, cartilage, epiphyseal bone, bronchial epithelial cells, and connective tissue cells in the dermis. By in situ hybridization, group II PLA2 mRNA was localized in hepatocytes, epidermal cells, dermal cells, connective tissue fibroblasts, epithelial and smooth muscle cells of the urinary bladder, and cells of Bowman's capsule. These results show that human group II PLA2 is expressed in large amounts in hepatocytes and many extrahepatic tissues of the transgenic mice. These animals provide a useful new tool for studies on the metabolism, in vivo effects, and physiological and pathological roles of phospholipase A2.

Animals↗

PubMed1991

Eicosanoid generation from antigen-primed mast cells by extracellular mammalian 14-kDa group II phospholipase A2.

The extracellular form of 14-kDa group II phospholipase A2 has been found to accumulate at various types of inflammatory sites. In the present paper, we have studied the possible role of the extracellular 14-kDa group II phospholipase A2 in the process of prostaglandin production in activated rat mast cells. When mast cells obtained from the peritoneal cavity of rats were sensitized with IgE, challenged with antigen and then exposed to extracellular 14-kDa group II phospholipase A2, appreciable release of prostaglandin D2 was observed. Generation of prostaglandin D2 was dependent on the concentration of the phospholipase A2 as well as that of the antigen, while no appreciable prostaglandin D2 generation was observed with cells in the absence of the antigen. No histamine release was observed under the same conditions. Phosphatidylcholine in mast cell membranes was appreciably hydrolyzed to liberate free arachidonic acid when mast cells were incubated with 14-kDa group II phospholipase A2 added exogenously in the presence of the antigen. Both the generation of prostaglandin D2 and the release of arachidonic acid were retarded by inhibitors specific to 14-kDa group II phospholipase A2. Thus, 14-kDa group II phospholipase A2 may function in the process of inflammation by acting on IgE-antigen-primed mast cells, which are not fully activated, to generate eicosanoids.

Animals↗

PubMed1990

Structure of gene coding for rat group II phospholipase A2.

The gene coding for rat group II phospholipase A2 was isolated from a rat genomic library by using the cDNA for rat platelet phospholipase A2 as a hybridization probe. The rat group II phospholipase A2 gene spanned about 3.5 kilobase pairs and consisted of five exons. Southern blot analysis revealed that a single copy of this gene exists in the rat haploid genome. A TATA-like sequence and two AP-2 binding site-like loci were found upstream from the tentatively identified transcription initiation site.

Amino Acid Sequence↗

PubMed2000

Resistance of transgenic mice expressing human group II phospholipase A2 to Escherichia coli infection.

Group II phospholipase A2 (PLA2) is a newly recognized antibacterial acute-phase protein. Recently we observed that transgenic mice expressing group II PLA2 (PLA2(+) mice) were able to resist experimental Staphylococcus aureus infection by killing the bacteria, as indicated by improved survival and by the small numbers of live bacteria in their tissues (V. J. O. Laine, D. S. Grass, and T. J. Nevalainen, J. Immunol. 162:7402-7408, 1999). To establish the role of group II PLA2 in Escherichia coli infection, the host responses of PLA2(+) mice and their PLA2-deficient C57BL/6J littermates (PLA2(-) mice) were studied after intraperitoneal administration of E. coli. The levels of group II PLA2 in sera of PLA2(+) mice increased after the administration of E. coli, and the concentration of group II PLA2 correlated significantly with the catalytic activity of PLA2 in serum. PLA2(+) mice showed lower rates of mortality and less bacterial growth in peritoneal lavage fluid, blood, and spleen and liver tissues than PLA2(-) mice. Unlike the observations with staphylococcal infection, serum and peritoneal lavage fluid did not inhibit the growth of E. coli in vitro. The results indicate that expression of the group II PLA2 transgene improves the host defense of mice against E. coli infection.

Animals↗

PubMed1997

Half-life of interleukin-1 beta-induced group II phospholipase A2 in rat mesangial cells.

Group II phospholipase A2 (sPLA2) has been implicated as an important agent involved in a number of inflammatory processes. Potent pro-inflammatory cytokines, such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) have been found to induce sPLA2 synthesis and release from many cell types among which mesangial cells. Although considerable research has been devoted to unravelling the mechanisms underlying the induction of sPLA2 not much is known about the time scale at which the cytokine elicited signals for sPLA2 induction persist in target cells. In this study we addressed that question by using rat renal mesangial cells as a model target cell. We found that after removal of IL-1 beta from the culture medium, the induced-sPLA2 synthesis continues at gradually decreasing rates for approximately 8 h. This is accompanied by a decrease in sPLA2 mRNA levels. Furthermore, with pulse-chase experiments we investigated the half-life of sPLA2 disappearance from the cells. This disappearance was found to be biphasic. A rapidly disappearing pool, constituting approx. 74% of the total, exhibited a half-life of 1.6 +/- 0.2 h. The remaining pool of the induced enzyme was much more stable and its level remained constant for at least 24 h. Analysis of the appearance of newly synthesized enzyme in the culture medium indicated this process to be completed in an hour.

Animals↗

PubMed2006

Prognostic value of phospholipase A2 group II, C-reactive protein and Simplified Acute Physiological Score II in intensive care patients.

We investigated the prognostic value of group II phospholipase A2 (PLA2-II) and C-reactive protein (CRP) in patients of the intensive care unit (ICU) who developed severe inflammatory reaction. In addition, the biochemical markers were correlated with the Simplified Acute Physiological Score II (SAPS II). Our study comprised 40 patients with multiple injuries and 35 patients with sepsis admitted to the ICU, and assessed during a follow-up of as long as 28 days. There were 18 survivors and 17 non-survivors in the sepsis group, and 22 survivors and 18 nonsurvivors in the group of patients with multiple injuries. In the group of patients with multiple injuries, the intensity of host inflammatory response showed clearly distinct PLA2-II and CRP profiles: the overall levels of PLA2-II and CRP were significantly higher in non-survivors than in survivors. PLA2-II and CRP do not discriminate nonsurvivors from survivors with sepsis. ROC (receiver operating characteristic curve) analysis and the area under the curve (AUC) showed the best classification of polytrauma patients with SAPS II and PLA2-II. In the group of patients with sepsis, only SAPS II appeared to be the most helpful predictive measure regarding patient outcome.

Adult↗

PubMed1994

Exogenous group II phospholipase A2 induces prostaglandin E2 production in mouse peritoneal macrophages.

Cultures of mouse peritoneal resident macrophages produced prostaglandin E2 when exposed to extracellular group II phospholipase A2. The response to group II phospholipase A2 was concentration dependent, and prostaglandin E2 production in response to 1 microgram/ml purified group II enzyme was comparable to the maximal response elicited by lipopolysaccharide. Group II phospholipase A2 required millimolar concentrations of extracellular Ca2+ for the induction of prostaglandin E2 production, as well as for phospholipase A2 activity. YM-26734 (4-(3,5-didodecanoyl-2,4,6-trihydroxyphenyl)-7-hydroxy-2-(4-hydroxyph eny l) chroman), a selective inhibitor of group II phospholipase A2, inhibited not only the enzyme activity but also the prostaglandin E2 production-inducing activity of group II phospholipase A2 in a concentration-dependent manner. These findings suggest that group II phospholipase A2 released into the extracellular space may induce prostaglandin E2 production through hydrolysis of plasma membrane phospholipids. Taken together with the previous finding that YM-26734 suppressed inflammatory responses in vivo, these results suggest that group II phospholipase A2 may play a role in the excitation and/or progression of inflammatory processes through the production of eicosanoids.

Animals↗

PubMed1996

Zinc (Zn2+) binds to and stimulates the activity of group I but not group II phospholipase A2.

Phospholipase A2 plays an important part in the generation of inflammatory lipid mediators and so it is of major interest to understand functional distinctions between structurally similar forms of phospholipase A2. In the present study, the influence of zinc (Zn2+) on the activity of group I and group II phospholipase A2 was examined in vitro. It appeared that Zn2+ (0.04-1 x 10(-3)M) increased group I phospholipase A2 activity from porcine pancreas and rat lung whereas the activity of group II phospholipase A2 from Crotalus atrox and Vipera russelli was unaffected. The presence of Cd2+ of Hg2+ (0.8-5 x 10(-3)M) also increased group I pancreatic phospholipase A2 activity while no augmentation was found with Cr2+, Fe2+ or Mg2+. The selective stimulation of group I phospholipase A2 by Zn2+ corresponded to a binding of these phospholipases A2 to a zinc-affinity column, while group II phospholipase A2 was not bound. Furthermore, the PLA2 activity in bronchoalveolar lavage fluid from rat was stimulated by Zn2+. These results indicate that Zn2+ binds to and increases the activity of group I, but not group II phospholipase A2. This difference in Zn(2+)-binding may be used to discriminate between group I and group II phospholipase A2 and to separate the enzymes from each other in complex biological materials. The possibility that activation of group I phospholipase A2 in the lung is important in zinc-induced metal fume fever is implied.

Animals↗

PubMed1997

Flavonoids as phospholipase A2 inhibitors: importance of their structure for selective inhibition of group II phospholipase A2.

The inhibitory effect of the plant flavonoid, rutin, on group I phospholipase A2 (PLA2-I) from porcine pancreas and Naja naja, and on group II phospholipase A2 (PLA2-II) from Vipera russelli and Crotalus atrox was investigated. Rutin efficiently inhibited PLA2-II from both Vipera russelli and Crotalus atrox but was only a weak inhibitor of PLA2-I from porcine pancreas and Naja naja. The lack of strong inhibition of pancreatic PLA2-I was not due to contaminating proteins in the enzyme preparation, since the same weak inhibition was obtained against pancreatic PLA2 purified to homogeneity as judged by two-dimensional gel electrophoresis. Rutin also efficiently inhibited human PLA2-II from synovial fluid but was only a weak inhibitor of human PLA2-I from pancreatic juice, suggesting that rutin is a selective PLA2-I from porcine pancreas. The results obtained indicate that the hydroxyl group in 5-position as well as the double bond and the double-bonded oxygen in the oxane ring are all important for the overall ability of flavonoids to inhibit PLA2 activity, and that the hydroxyl groups in 3'- and 4'- position are required for selective inhibition of PLA2-II.

Animals↗

PubMed1993

Group I and group II phospholipases A2 in serum in uraemia.

Time-resolved fluoroimmunoassays were used for the detection of pancreatic group I and synovial-type group II phospholipases A2 in sera of patients suffering from chronic renal failure before and after haemodialysis. The concentration of group I phospholipase A2 was ten-fold higher in sera of uraemic patients than in healthy controls. There was no significant difference in the concentrations of group I phospholipase A2 in serum before and after haemodialysis. The concentration of group II phospholipase A2 was only marginally increased in sera of uraemic patients, compared with healthy controls. There was no significant difference in the concentrations of group II phospholipase A2 before and after haemodialysis. The results indicate that the metabolism of group I phospholipase A2 differs from that of group II phospholipase A2 in chronic renal failure.

Adult↗

PubMed1994

Levels and localization of group II phospholipase A2 and annexin I in interleukin- and dexamethasone-treated rat mesangial cells: evidence against annexin mediation of the dexamethasone-induced inhibition of group II phospholipases A2.

The mechanism by which glucocorticosteroids inhibit the synthesis and secretion of pro-inflammatory arachidonate metabolites is still controversial. Initially it was postulated that glucocorticoids can induce the formation of PLA2 inhibitory proteins termed annexins. We have previously shown that the cytokine-induced 14 kDa PLA2 activity and the synthesis of prostaglandin E2 in rat mesangial cells is dose-dependently blocked by pretreatment of the cells with dexamethasone (Schalkwijk et al. (1991) Biochem. Biophys. Res. Commun. 180, 46-52). Concurrently, the synthesis of 14 kDa group II PLA2 is suppressed. The regulation of PLA2 activity is complex and may well involve superimposable mechanisms. Thus, although the decrease in PLA2 protein levels could in itself explain the dexamethasone-induced decrease in PLA2 activity, a contribution of the glucocorticoid-induced anti-phospholipase A2 protein annexin cannot be ruled out a priori. To investigate this possibility we analyzed the level of annexin I by Western blotting and immunostaining in mesangial cells treated with interleukin-1 beta and/or dexamethasone. Under conditions where 14 kDa group II PLA2 activity and protein levels were dramatically affected by interleukin-1 and dexamethasone, the level of annexin I in the cells remained constant. Dexamethasone also did not induce the secretion of annexin I. In addition, no evidence for dexamethasone-induced translocation of annexin I from the cytosol to membranes, thereby possibly sequestering the substrates for PLA2, was obtained. Immunofluorescence studies localized the cytokine-induced PLA2 to the Golgi area and punctate structures in the cytoplasm. We have also studied the subcellular localization of annexin I in rat mesangial cells using confocal microscopy. These studies located annexin I mainly in the cytoplasma and the nucleus. We conclude from these experiments that the dexamethasone-induced inhibition of 14 kDa group II PLA2 in rat mesangial cells is not mediated by annexin I and is solely due to the suppression of PLA2 gene expression.

Animals↗

PubMed1998

Elevated group II phospholipase A2 mass concentration in serum and colonic mucosa in Crohn's disease.

Group II phospholipase A2 has been proposed to play an important role in the pathophysiology of inflammatory bowel diseases. This enzyme has also been linked to host defence mechanisms against bacteria. The current study aimed at measuring the mass concentrations of group II phospholipase A2 in serum and colonic mucosa of patients with Crohn's disease of different severity and of appropriate control patients without any inflammatory disease. The activity of the disease was determined by clinical factors (the simple index score) and endoscopic and histological scoring. The mass concentration of group II phospholipase A2 was measured by a time-resolved fluoroimmunoassay. The mass concentrations of group II phospholipase A2 in serum and colonic mucosa were significantly higher both in patients with active and inactive Crohn's disease when compared with controls. There was statistically significant difference in the mass concentration of group II phospholipase A2 in colonic mucosa but not in serum between inactive and active Crohn's disease. The current results indicate that the mass concentration of group II phospholipase A2 is increased in serum and colonic mucosa of patients with Crohn's disease and that the latter is associated with the degree of the inflammatory activity in the intestinal wall. These results support the idea that group II phospholipase A2 is involved in the local and generalised pathological processes of Crohn's disease.

Adolescent↗

PubMed1994

Group II phospholipase A2 in serum in critically ill surgical patients.

OBJECTIVE: To study the association of increased serum group II phospholipase A2 concentrations to C-reactive protein concentrations in the sera of critically ill surgical patients. DESIGN: Prospective study. SETTING: Surgical intensive care unit (ICU) of a university hospital. PATIENTS: Sixty-seven consecutive patients admitted to the surgical ICU. INTERVENTIONS: The catalytic activity of phospholipase A2 and the serum concentrations of group II phospholipase A2 and C-reactive protein were measured daily during each patient's stay in the ICU. A total of 205 blood samples were taken. In addition, the preoperative serum levels of group II phospholipase A2 were determined in patients admitted for cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Serum group II phospholipase A2 values correlated statistically significantly with the catalytic activity of phospholipase A2 and serum C-reactive protein values. In particular, severe infections, diseases involving tissue destruction, and elective operations per se, caused considerable increases in serum group II phospholipase A2 concentrations. CONCLUSION: Our results support the earlier presented idea that group II phospholipase A2 is an acute-phase reactant.

Acute-Phase Proteins↗

PubMed2000

Distribution of group II phospholipase A2 protein and mRNA in rat tissues.

Group II phospholipase A2 (PLA2) is an acute-phase protein and an important component of the host defense against bacteria. In this study we investigated the distribution of PLA2 protein by immunohistochemistry and the distribution of mRNA of PLA2 by Northern blotting and in situ hybridization in rat tissues. PLA2 protein was localized in the Paneth cells of the intestinal mucosa, chondrocytes and the matrix of cartilage, and megakaryocytes in the spleen. By Northern blotting, mRNA of PLA2 was found in the gastrointestinal tract, lung, heart, and spleen. By in situ hybridization, PLA2 mRNA was localized in the Paneth cells of the small intestinal mucosa but in no other cell types. Our results show specific distribution of PLA2 in a limited number of cell types in rat tissues. The reagents developed in this study (the anti-rat PLA2 antibody and probes for Northern blotting and in situ hybridization of mRNA of rat PLA2) will provide useful tools for future studies concerning the role of PLA2 in various experimental disease models.

Amino Acid Sequence↗

PubMed1997

Group II phospholipase A2 as an autocrine growth factor mediating interleukin-1 action on mesangial cells.

The proliferation of mesangial cells plays a central role in the progression of glomerulonephritis. We studied the role of group II phospholipase A2 in interleukin-1-stimulated proliferation of mesangial cells. Cultured rat mesangial cells secreted 5.3 units group II phospholipase A2/24 h per 10(5) cells in response to stimulation of 200 U/ml of interleukin-1. Northern hybridization analysis showed that mRNA for group II phospholipase A2 was induced by exogenously added group II phospholipase A2 (15 U/ml) as well as interleukin-1. The pretreatment of quiescent mesangial cells with interleukin-1 augmented [3H]thymidine incorporation caused by platelet derived growth factor. Exogenous group II phospholipase A2 (5-36 U/ml) purified homogeneously from rat spleen also increased [3H]thymidine incorporation by platelet derived growth factor-stimulated mesangial cells in a dose dependent manner (36 U/ml phospholipase A2; 1.9-fold). The stimulatory effect of interleukin-1 on DNA synthesis of mesangial cells was specifically blunted by immunoglobulin raised against group II phospholipase A2. Group II phospholipase A2 (16 U/ml) amplified a platelet derived growth factor-stimulated increase in the mesangial cell number by 1.5-fold. Among the products of the phospholipase A2-catalyzed reaction, lysophospholipids including lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidic acid, but not fatty acids, mimicked the stimulatory effect of interleukin-1 and phospholipase A2. These results suggest that group II phospholipase A2 acts as a signaling molecule that mediates interleukin-1-induced growth of rat mesangial cells through yielding lysophospholipids.

Animals↗