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

Positive affinity chromatography on heparin-Sepharose has proved a most crucial step in the purification of pregnancy-associated plasma protein A (PAPP-A). In this chromatographic procedure, PAPP-A was purified almost 500-fold from term pregnancy serum. Further purification was achieved by gel filtration and negative immunoaffinity chromatography. Both PAPP-A and free heparin inhibited granulocyte elastase (HGE) activity. Whereas free heparin inhibited only in hypotonic buffers, PAPP-A inhibited HGE in hypertonic buffers also. However, PAPP-A did not inhibit other proteases (trypsin, chymotrypsin, plasmin, fibroblast collagenase) or proteolytic cascades (complement activation). Since heparin was not detected in the purified PAPP-A, the inhibition of HGE was not due to desorbed or leeched heparin ligand.
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PMID:Pregnancy-associated plasma protein A interaction with heparin: a critical appraisal. 172 Oct 35

By sensitive and specific radioimmunoassays PAPP-A and PP5 were detected in follicular aspirates obtained from women undergoing ovarian hyperstimulation for oocyte harvest prior to in vitro fertilization and embryo transfer. Follicular and pregnancy-derived PAPP-A were immunologically and physicochemically indistinguishable. Similarly, pregnancy- and nonpregnancy-derived PP5 were immunologically indistinguishable. However, in addition to the 18- and 36-K species, a larger species having a molecular size greater than 140K was found in the follicular fluid. Mean follicular PAPP-A and PP5 concentrations were 727 mIU/L and 1376 mAU/L, respectively, with no significant correlation between follicular PAPP-A, PP5, and steroid concentrations. There was, however, a significant but negative relationship with follicular volume. Preliminary in vitro studies indicated that both proteins were synthesized by granulosa cells in preparation for follicular rupture. Follicular PP5, like antithrombin III, interacted reversibly with heparin and thrombin affinity matrices, suggesting a potential biological role as a follicular anticoagulant, whereas PAPP-A, a specific and potent inhibitor of leukocyte elastase, contributes to the maintenance of proteolytic homeostasis and the protection of spermatozoa and embryo against proteolytic attack originating from the maternal leukocytes.
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PMID:Pregnancy-associated plasma protein-A and placental protein 5 in human ovarian follicular fluid. 240 57

Placentae obtained from RU 486 treated cynomolgus monkeys, with successful pregnancy outcome, could not be distinguished, by microscopic or macroscopic examination, from normal placental morphology of untreated females. However, circulating PAPP-A levels were markedly depressed in RU 486 treated (114.8 +/- 13.1 IU/l) than in control animals (477.2 +/- 150 IU/l), suggesting compromised placental physiology. Microscopic examination of placental tissue obtained from animals with fetal demise, after RU 486 administration, revealed pathological changes. When fetal demise occurred recently (less than 24 h), active villus destruction by infiltrating polymorphonuclear leukocytes was readily observed. Whereas aqueous extracts of placentae, whether obtained by cesarean section or spontaneous delivery, inhibited neutrophil elastase (HGE) activity, extracts of placenta being degraded by host phagocytic-proteolytic defense system were rich in HGE activity. Thus suggesting that parturition was not mediated by leukocyte lysosomal proteases, such as HGE, and that hemochorrially implanted placentae produce PAPP-A, a specific inhibitor of HGE. Administration of RU 486 decreased placental PAPP-A production and secretion, culminating with a neutrophilic infiltration into placental intervillous blood spaces, destruction of villus structure and fetal demise.
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PMID:RU 486 mediated leukocytic inflammatory reaction at the utero-placental interface. 248 46