Isolation and Characterization of cDNA Clones from Human Placenta Coding for Phospholipase A2

Crowl, Robert M.; Stoner, Cheryl R.; Stoller, Tim; Pan, Yu‐Ching E.; Conroy, Robert R.

doi:10.1007/978-1-4613-0651-1_11

Cited by 23 publications

(12 citation statements)

References 32 publications

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“…In contrast to the PLA2 receptor, the putative UG receptor appears to be a nonglycosylated protein. These novel findings are more significant when considered together with the facts that an extracellular PLA2 cDNA from human placenta (59) has been cloned and characterized and structural similarity between UG and an extracellular PLA2 (60) has been reported. Molecular characterization of UG and PLA2 receptors and their regulation of expression in the uterine cells during pregnancy may yield vital information regarding the physiological regulatory role(s) of these two important classes of proteins.…”

Section: Ug Immunofluorescence In Rabbit Fetal Lungmentioning

confidence: 90%

Uteroglobin gene expression in the rabbit uterus throughout gestation and in the fetal lung. Relationship between uteroglobin and eicosanoid levels in the developing fetal lung.

Peri¹,

Dubin²,

Dhanireddy³

et al. 1995

J. Clin. Invest.

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Uteroglobin (UG) gene encodes a cytokine-like, multifunctional, antiinflammatory protein, with potent phospholipase A2-inhibitory activity. It has been suggested that during implantation this protein protects the embryos from maternal immunological assault, facilitates the maintenance of quiescence in the uterus throughout pregnancy, prevents the onset of premature labor, and helps maintain an inflammationfree respiratory organ. This latter function of UG is suggested to be accomplished by preventing hydrolysis of surfactant phospholipids by a lung-specific phospholipase A2. Using reverse transcription polymerase chain reaction, in situ hybridization, immunofluorescence, and radioimmunoassay, we studied UG gene expression in the rabbit uterus throughout gestation and in the fetal lung. Here, we report that: (a) contrary to previous reports, UG gene expression in the rabbit uterus occurs throughout gestation with a precipitous decline just before parturition; (b) this gene expression is dramatically increased in the fetal lung with increasing gestational age; and (c) while there is an inverse relationship between the levels of UG, PGE2, and PGF2., a positive correlation was found in that of UG and leukotriene C4 in the fetal lung. Our results raise the possibility that dysregulation of UG gene expression, at least in part, may contribute to the onset of premature labor and the development of inflammatory lung disease in premature neonates. (J. Clin. Invest. 1995. 96:343-353.)

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Section: Ug Immunofluorescence In Rabbit Fetal Lungmentioning

confidence: 90%

Uteroglobin gene expression in the rabbit uterus throughout gestation and in the fetal lung. Relationship between uteroglobin and eicosanoid levels in the developing fetal lung.

Peri¹,

Dubin²,

Dhanireddy³

et al. 1995

J. Clin. Invest.

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“…For the analysis of sPLA 2 -IIA mRNA, oligonucleotides were synthesized according to the published nucleotide sequence of human placental sPLA 2 -IIA cDNA. 28 In the nested PCR, extrinsic and intrinsic primer pairs were applied in a final concentration of 0.1 mol/L and 0.8 mol/L, whereas in the conventional PCR, the final concentration averaged 0.8 mol/L. The conditions for amplification were as follows: 15 cycles at 94°C for 30 seconds and at 60°C for 50 seconds, followed by 40 cycles at 94°C for 30 seconds and at 72°C for 1 minute.…”

Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

Expression of Secretory Group IIA Phospholipase A ₂ in Relation to the Presence of Microbial Agents, Macrophage Infiltrates, and Transcripts of Proinflammatory Cytokines in Human Aortic Tissues

Menschikowski

Rosner-Schiering

Eckey

et al. 2000

ATVB

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Abstract-Recent seroepidemiological and immunohistochemical studies have demonstrated an association between microbial infections and atherosclerosis. However, the mechanisms underlying this association are widely unknown. In the present study, arterial specimens obtained at autopsy after sudden death were analyzed concerning (1) the presence of Chlamydia pneumoniae, cytomegalovirus, herpes simplex virus, and Helicobacter pylori; (2) the expression of secretory group IIA phospholipase A 2 (sPLA 2 -IIA) and of proinflammatory cytokines; and (3) the stage of atherosclerosis. Genomic DNA of microbial pathogens was determined by the polymerase chain reaction technique. The expression of sPLA 2 -IIA was studied immunohistochemically by using monoclonal antibodies against human sPLA 2 -IIA. Transcripts specific for sPLA 2 -IIA, interleukin-1␤, tumor necrosis factor-␣, and interferon-␥ were identified by reverse transcription-polymerase chain reaction. In 18 of 102 analyzed specimens, DNA of microbial pathogens was found. Thirteen sections were positive for C pneumoniae, whereas 2 specimens were positive either for cytomegalovirus or for herpes simplex virus. One section contained genomic DNA of all 3 pathogens simultaneously. None of the analyzed tissues exhibited nucleic acids specific for H pylori. In addition to macrophage infiltrates, the presence of microbial DNA was closely associated with the occurrence of transcripts specific for proinflammatory cytokines and sPLA 2 -IIA. Pathogens as well as sPLA 2 -IIA and cytokines were found to be present not only in advanced but also in early stages of atherosclerosis. In tissues negative for sPLA 2 -IIA and cytokine expression, none of the pathogens could be identified. Because macrophages exposed to phospholipase A 2 -treated lipoproteins are transformed into foam cells in vitro, the results of this study suggest an alternative mechanism by which microbial infections may act in a proatherogenic fashion in vessel walls.

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“…This region is also highly conserved in mammalian group II PLA2s, which have been suggested to be involved in several important human diseases (28). X-ray crystallographic data on recombinant human synovial PLA2 have confirmed that the structure ofthis enzyme is similar to that ofthe pancreatic and snake venom PLA2s (29).…”

Section: Resultsmentioning

confidence: 83%

“…The region of phospholipase A2 (residues [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] recognized by this antibody includes a highly conserved sequence which contains several functionally important residues of both group I and group U phospholipases A2. These data suggest that amino acid residues in this region of porcine pancreatic phospholipase A2 are accessible for interaction with inhibitors such as neutalizing antibodies and that agents specifically interacting with this region may have potent phospholipase A2 inhibitory activity.…”

mentioning

confidence: 99%

Identification of a specific region of low molecular weight phospholipases A2 (residues 21-40) as a potential target for structure-based design of inhibitors of these enzymes.

Cordella‐Miele¹,

Miele²,

Mukherjee³

1993

Proc. Natl. Acad. Sci. U.S.A.

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We have identified a specific region ofporcine pancreatic phospholipase A2 (residues 21-40) which interacts with a neutralizing antibody causing a dramatic inhibition ofits enzymatic activity (K1 in the order of 10-8 M). The binding equilibrium of the antibody-phospholipase A2 complex is reached in <3 min at 37C. Fab fragments are equally effective phospholipase A2 inhibitors, as are intact IgG molecules. The inhibition is virtually complete and noncompetitive with respect to phosphatidylcholine substrate. The formation of precipitating immunocomplexes is not involved in the inhibition.The region of phospholipase A2 (residues 21-40) recognized by this antibody includes a highly conserved sequence which contains several functionally important residues of both group I and group U phospholipases A2. These data suggest that amino acid residues in this region of porcine pancreatic phospholipase A2 are accessible for interaction with inhibitors such as neutalizing antibodies and that agents specifically interacting with this region may have potent phospholipase A2 inhibitory activity. Thus, this conserved region of low molecular weight, extracellular phospholipases A2 'is a potential target for structure-based design of specific noncompetitive inhibitors of these enzymes. Since these extracellular phospholipases A2 are suggested to play a pathogenic role in several important human diseases, the development of such pharmacologic inhibitors is of potential clinical importance.

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Isolation and Characterization of cDNA Clones from Human Placenta Coding for Phospholipase A2

Cited by 23 publications

References 32 publications

Uteroglobin gene expression in the rabbit uterus throughout gestation and in the fetal lung. Relationship between uteroglobin and eicosanoid levels in the developing fetal lung.

Uteroglobin gene expression in the rabbit uterus throughout gestation and in the fetal lung. Relationship between uteroglobin and eicosanoid levels in the developing fetal lung.

Expression of Secretory Group IIA Phospholipase A ₂ in Relation to the Presence of Microbial Agents, Macrophage Infiltrates, and Transcripts of Proinflammatory Cytokines in Human Aortic Tissues

Identification of a specific region of low molecular weight phospholipases A2 (residues 21-40) as a potential target for structure-based design of inhibitors of these enzymes.

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Isolation and Characterization of cDNA Clones from Human Placenta Coding for Phospholipase A2

Cited by 23 publications

References 32 publications

Uteroglobin gene expression in the rabbit uterus throughout gestation and in the fetal lung. Relationship between uteroglobin and eicosanoid levels in the developing fetal lung.

Uteroglobin gene expression in the rabbit uterus throughout gestation and in the fetal lung. Relationship between uteroglobin and eicosanoid levels in the developing fetal lung.

Expression of Secretory Group IIA Phospholipase A 2 in Relation to the Presence of Microbial Agents, Macrophage Infiltrates, and Transcripts of Proinflammatory Cytokines in Human Aortic Tissues

Identification of a specific region of low molecular weight phospholipases A2 (residues 21-40) as a potential target for structure-based design of inhibitors of these enzymes.

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Expression of Secretory Group IIA Phospholipase A ₂ in Relation to the Presence of Microbial Agents, Macrophage Infiltrates, and Transcripts of Proinflammatory Cytokines in Human Aortic Tissues