The Experts below are selected from a list of 7383 Experts worldwide ranked by ideXlab platform
Alicia Torriglia - One of the best experts on this subject based on the ideXlab platform.
-
the hidden side of serpinb1 leukocyte Elastase Inhibitor
Seminars in Cell & Developmental Biology, 2017Co-Authors: Alicia Torriglia, Imene Jaadane, Elisabeth MartinAbstract:SERPINB1, also called Leukocyte Elastase Inhibitor (LEI) is a member of the clade B of SERPINS. It is an intracellular protein and acts primarily to protect the cell from proteases released into the cytoplasm during stress. Its role in inflammation is clear due to its involvement in the resolution of chronic inflammatory lung and bowel diseases. LEI/SERPINB1 intrinsically possesses two enzymatic activities: an antiprotease activity dependent on its reactive site loop, which is analogous to the other proteins of the family and an endonuclease activity which is unveiled by the cleavage of the reactive site loop. The conformational change induced by this cleavage also unveils a bipartite nuclear localization signal allowing the protein to translocate to the nucleus. Recent data indicate that it has also a role in cell migration suggesting that it could be involved in diverse processes like wound healing and malignant metastases.
-
Increase in the expression of leukocyte Elastase Inhibitor during wound healing in corneal endothelial cells
Cell and Tissue Research, 2015Co-Authors: Cristian Justet, Alicia Torriglia, Frances Evans, Silvia ChiffletAbstract:Tissue injury triggers a complex network of cellular and molecular responses. Although cell migration and proliferation are the most conspicuous, several other responses, such as apoptosis and increased protease activity, are necessary for a proper restitution of the tissue. In this work, we study the leukocyte Elastase Inhibitor (LEI) expression during wound healing of bovine corneal endothelial monolayers in culture. LEI is a multifunctional protein with anti-protease and anti-apoptotic activity. When properly cleaved, it is transformed into L-DNase II, a pro-apoptotic enzyme and translocated to the nucleus. We found that early after injury LEI increases its protein and mRNA expressions, without nuclear translocation and returns to basal levels immediately after wound closure. This increase is blocked by N-acetylcysteine, suggesting that production of reactive oxygen species immediately after wounding is involved in the LEI increase. Another finding of this work is that there is an acidification of the cells at the wound border which, in contrast to other cell types, does not determine nuclear translocation of the protein. Taken together, the results of this work suggest that the function of LEI during wound healing is related to its activity as a protease Inhibitor and/or to its anti-apoptotic activity.
-
interaction of leukocyte Elastase Inhibitor l dnase ii with bcl 2 and bax
Biochimica et Biophysica Acta, 2014Co-Authors: Imene Jaadane, Atf Nagbou, Francine Beharcohen, Alicia TorrigliaAbstract:Abstract Leukocyte Elastase Inhibitor (LEI, also called serpin B1) is a protein involved in apoptosis among other physiological processes. We have previously shown that upon cleavage by its cognate protease, LEI is transformed into L-DNase II, a protein with a pro-apoptotic activity. The caspase independent apoptotic pathway, in which L-DNase II is the final effector, interacts with other pro-apoptotic molecules like Poly-ADP-Ribose polymerase (PARP) or Apoptosis Inducing Factor (AIF). The screening of LEI/L-DNase II interactions showed a possible interaction with several members of the BCL-2 family of proteins which are known to have a central role in the regulation of caspase dependent cell death. In this study, we investigated the regulation of LEI/L-DNase II pathway by two members of this family of proteins: BAX and BCL-2, which have opposite effects on cell survival. We show that, in both BHK and HeLa cells, LEI/L-DNase II can interact with BCL-2 and BAX in apoptotic and non-apoptotic conditions. These proteins which are usually thought to be anti-apoptotic and pro-apoptotic respectively, both inhibit the L-DNase II pro-apoptotic activity. These results give further insight in the regulation of caspase independent pathways and highlight the involvement of the intracellular environment of a given protein in the determinism of its function. They also add a link between caspase-dependent and independent pathways of apoptosis.
-
apoptosis inducing factor aif and leukocyte Elastase Inhibitor l dnase ii lei ldnaseii can interact to conduct caspase independent cell death
Apoptosis, 2013Co-Authors: Chloé Leprêtre, Alicia Torriglia, Guergana Tchakarska, Hounayda Blibech, Cecile LebonAbstract:Programmed cell death is an important factor in tissue homeostasis. Lot of work has been performed to characterize the caspase-dependent cell death. Caspase-independent cell death, although important in many physiological situations, is less investigated. In this work we show that two caspase-independent effectors of cell death, namely apoptosis-inducing factor and leukocyte Elastase Inhibitor derived DNase II interact and can cooperate to induce cell death. These results contribute to the knowledge of molecular pathways of cell death, an important issue in the development of new therapeutic strategies for the treatment of cancer or neurodegenerative diseases.
-
leukocyte Elastase Inhibitor a new regulator of parp 1
Annals of the New York Academy of Sciences, 2009Co-Authors: Chloé Leprêtre, Alicia Torriglia, Giuseppina Sidoli, Ivana A ScovassiAbstract:Poly(ADP-ribose) polymerase-1 (PARP-1) uses NAD(+) as a substrate to form ADP-ribose. During apoptosis, caspases cleave PARP-1 to avoid excessive NAD consumption. Because PARP-1 is a key regulator of the activity of DNases involved in caspase-dependent apoptosis, its cleavage is required to promote DNA degradation. To explore the situation in caspase-independent cell death, we investigated the effect of PARP-1 on the acid endonuclease leukocyte Elastase Inhibitor (LEI)-derived DNase II (L-DNase II). We found for the first time an association between PARP-1 and LEI/L-DNase II. Unexpectedly, we observed that LEI influenced the automodification of PARP-1.
Chloé Leprêtre - One of the best experts on this subject based on the ideXlab platform.
-
apoptosis inducing factor aif and leukocyte Elastase Inhibitor l dnase ii lei ldnaseii can interact to conduct caspase independent cell death
Apoptosis, 2013Co-Authors: Chloé Leprêtre, Alicia Torriglia, Guergana Tchakarska, Hounayda Blibech, Cecile LebonAbstract:Programmed cell death is an important factor in tissue homeostasis. Lot of work has been performed to characterize the caspase-dependent cell death. Caspase-independent cell death, although important in many physiological situations, is less investigated. In this work we show that two caspase-independent effectors of cell death, namely apoptosis-inducing factor and leukocyte Elastase Inhibitor derived DNase II interact and can cooperate to induce cell death. These results contribute to the knowledge of molecular pathways of cell death, an important issue in the development of new therapeutic strategies for the treatment of cancer or neurodegenerative diseases.
-
leukocyte Elastase Inhibitor a new regulator of parp 1
Annals of the New York Academy of Sciences, 2009Co-Authors: Chloé Leprêtre, Alicia Torriglia, Giuseppina Sidoli, Ivana A ScovassiAbstract:Poly(ADP-ribose) polymerase-1 (PARP-1) uses NAD(+) as a substrate to form ADP-ribose. During apoptosis, caspases cleave PARP-1 to avoid excessive NAD consumption. Because PARP-1 is a key regulator of the activity of DNases involved in caspase-dependent apoptosis, its cleavage is required to promote DNA degradation. To explore the situation in caspase-independent cell death, we investigated the effect of PARP-1 on the acid endonuclease leukocyte Elastase Inhibitor (LEI)-derived DNase II (L-DNase II). We found for the first time an association between PARP-1 and LEI/L-DNase II. Unexpectedly, we observed that LEI influenced the automodification of PARP-1.
-
leukocyte Elastase Inhibitor a new regulator of parp 1
Annals of the New York Academy of Sciences, 2009Co-Authors: Chloé Leprêtre, Alicia Torriglia, Giuseppina Sidoli, Ivana A ScovassiAbstract:as a substrate to for m A DP-ribose .During apoptosis , caspases clea ve P A RP-1 to avoid ex cessiv e N A D consumption. B e-cause P ARP-1 is a k ey reg ulator o f the activity of DNases in vo lv ed in caspase-de pendentapoptosis ,its clea va ge is required to promote D N A de g radation. T o ex plore the situationin caspase-inde pendent cell death, w e in vestigated the effect o f P ARP-1 o n the acid en-don u clease leuk ocyte Elastase Inhibitor (LEI)Ðderiv ed DNase II (L-DNase II). W e foundfor the Þr st time an association b etw een P A RP-1 and LEI/L-DNase II. Une x pectedl y,w eobser ved that LEI insuenced the a utomodiÞcation of P A RP-1.Key words: apoptosis; L-DNase II; LEI; P A RP-1; p ol y(ADP-ribosylation)
-
regulation of poly adp ribose polymerase 1 functions by leukocyte Elastase Inhibitor lei derived dnase ii during caspase independent apoptosis
The International Journal of Biochemistry & Cell Biology, 2009Co-Authors: Chloé Leprêtre, Alicia Torriglia, A I Scovassi, G M ShahAbstract:Abstract Poly(ADP-ribose) polymerase-1 (PARP-1) is an important regulator of apoptosis. Its over-activation at the onset of apoptosis can inhibit the action of apoptotic endonucleases like caspase-activated DNase and DNAS1L3. Therefore, controlled PARP-1 proteolysis during caspase-dependent apoptosis is considered essential to promote DNA degradation. Yet, little is known about the interplay of PARP-1 and endonucleases that operate during caspase-independent cell death. Here we show that in the long-term cultured HeLa cells which undergo caspase-independent death, PARP-1 co-immunoprecipitates with leukocyte Elastase Inhibitor-derived DNase II (L-DNase II), an acid DNase implicated in this death pathway and activated by serine proteases. Our results indicate that, despite having putative poly(ADP-ribose)-acceptor sites, LEI/L-DNase II is neither significantly poly(ADP-ribosyl)ated nor inhibited by PARP-1 during caspase-independent apoptosis. Unexpectedly, caspase-independent apoptosis induced by hexa-methylene amiloride, LEI/L-DNase II can activate PARP-1 and promote its auto-poly(ADP-ribosyl)ation, thus inhibiting PARP-1 activity. Moreover, overexpression of LEI blocks the pro-survival effect of PARP-1 in this model of cell death. Our results provide the original evidence for a new mechanism of PARP-1 activity regulation in the caspase-independent death pathway involving LEI/L-DNase II.
-
leukocyte Elastase Inhibitor the precursor of l dnase ii inhibits apoptosis by interfering with caspase 8 activation
Biochimica et Biophysica Acta, 2008Co-Authors: Laura Padronbarthe, Chloé Leprêtre, Jacqueline Courta, Atf NagbouAbstract:Abstract LEI (Leukocyte Elastase Inhibitor), the precursor of the pro-apoptotic molecule L-DNase II, belongs to the ovalbumin subgroup of serpins. Several serpins can inhibit apoptosis: the viral serpin Crm A inhibits Fas or TNFα-induced apoptosis, and overexpression of PAI-2 or PI-9 protects cells from TNFα or granzyme B induced apoptosis. We have previously shown that LEI overexpression protects cells from etoposide-induced apoptosis. The molecular reason of this anti-apoptotic activity is now investigated. We show that, in BHK-21 and HeLa cells, LEI anti-protease activity is essential for its anti-apoptotic effect. The protease inhibited is cathepsin D, released from the lysosome during etoposide treatment. Cathepsin D enhances caspase activity in the cell by cleaving procaspase-8 and LEI overexpression slows down this cleavage, protecting cells from apoptosis. This let us presume that high expression of LEI in tumor cells may reduce the efficiency of etoposide as a chemotherapeutic agent.
Sumio Miyazaki - One of the best experts on this subject based on the ideXlab platform.
-
ulinastatin an Elastase Inhibitor inhibits the increased mrna expression of prostaglandin h2 synthase type 2 in kawasaki disease
The Journal of Infectious Diseases, 2000Co-Authors: Masafumi Zaitsu, Yuhei Hamasaki, Katsuya Tashiro, Muneaki Matsuo, Tomohiro Ichimaru, Ichiro Fujita, Hakaru Tasaki, Sumio MiyazakiAbstract:Kawasaki disease is an inflammatory disease of unknown cause that causes panvasculitis, including coronary arteritis. Polymorphonucleocytosis in the early stage of the illness suggests the implication of neutrophils in the pathogenesis of the disease. In the acute phase of Kawasaki disease, mRNA expression of prostaglandin H2 synthase (PHS)-2, as determined by reverse transcription-polymerase chain reaction, was markedly enhanced, and thromboxane A2 (TXA2)-synthesizing activity was increased in polymorphonuclear leukocytes (PMNL). This up-regulation of PHS-2 was suppressed by ulinastatin (a neutrophil-Elastase Inhibitor) treatment. Lipopolysaccharide-induced enhancement of PHS-2 mRNA was also inhibited by therapeutic doses of ulinastatin in vitro by use of PMNL from healthy volunteers. Thus, ulinastatin inhibits arachidonate PHS metabolism by inhibiting new induction of PHS-2 at the mRNA level, which is a novel pharmacologic action of this substance. Ulinastatin treatment is possibly an additional therapeutic approach to Kawasaki disease.
-
ulinastatin an Elastase Inhibitor inhibits the increased mrna expression of prostaglandin h2 synthase type 2 in kawasaki disease
The Journal of Infectious Diseases, 2000Co-Authors: Masafumi Zaitsu, Yuhei Hamasaki, Katsuya Tashiro, Muneaki Matsuo, Tomohiro Ichimaru, Ichiro Fujita, Hakaru Tasaki, Sumio MiyazakiAbstract:Kawasaki disease is an inflammatory disease of unknown cause that causes panvasculitis, including coronary arteritis. Polymorphonucleocytosis in the early stage of the illness suggests the implication of neutrophils in the pathogenesis of the disease. In the acute phase of Kawasaki disease, mRNA expression of prostaglandin H2 synthase (PHS)‐2, as determined by reverse transcription‐polymerase chain reaction, was markedly enhanced, and thromboxane A2 (TXA2)‐synthesizing activity was increased in polymorphonuclear leukocytes (PMNL). This up-regulation of PHS-2 was suppressed by ulinastatin (a neutrophil-Elastase Inhibitor) treatment. Lipopolysaccharide-induced enhancement of PHS-2 mRNA was also inhibited by therapeutic doses of ulinastatin in vitro by use of PMNL from healthy volunteers. Thus, ulinastatin inhibits arachidonate PHS metabolism by inhibiting new induction of PHS-2 at the mRNA level, which is a novel pharmacologic action of this substance. Ulinastatin treatment is possibly an additional therapeutic approach to Kawasaki disease. Kawasaki disease (mucocutaneous lymph node syndrome) is a febrile disease in early childhood that is characterized by high fever for 15 days, bilateral conjunctivitis, polymorphous rash, cervical lymphadenopathy, indurative edema of hands and feet followed by desquamation of skin, and changes in lips and mouth: reddened, dry or cracked lips, strawberry tongue, and diffuse redness of oral mucosa. The most important complication is coronary arteritis leading to the formation of aneurysm. Although the cause of Kawasaki disease is entirely unknown, many investigators speculate that viral, bacterial, or both types of infections are involved in some form in the beginning of the disease. In the early stage of the illness, laboratory examinations show polymorphonucleocytosis and marked elevation of levels of C-reactive protein (CRP) [1]. These findings are often accompanied by bacterial infection. Polymorphonucleocytosis in the acute phase of the disease suggests a possible implication of neutrophils in the inflammatory process in vascular lesions. Recent studies showed that numbers of lipopolysaccharide (LPS)‐positive polymorphonuclear leukocytes (PMNL), which were measured by flow cytometry by use of anti-LPS antibody, were increased and that plasma levels
Marlene Rabinovitch - One of the best experts on this subject based on the ideXlab platform.
-
overexpression of the serine Elastase Inhibitor elafin protects transgenic mice from hypoxic pulmonary hypertension
Circulation, 2002Co-Authors: Syed H E Zaidi, Xiaomang You, Sorana Ciura, Mansoor Husain, Marlene RabinovitchAbstract:Background— Increased serine Elastase activity has been implicated in the vascular remodeling associated with chronic hypoxia-related pulmonary hypertension in rats. Methods and Results— In this study we determined the time course of hypoxia-induced serine Elastase activity in the murine lung and related this to initiation of a proteolytic cascade characterized by an increase in matrix metalloproteinases (MMPs). We then used transgenic mice in which overexpression of the selective serine Elastase Inhibitor elafin was targeted to the cardiovascular system to determine whether upregulation of a naturally occurring serine Elastase Inhibitor suppresses MMPs and the hemodynamic and structural response to chronic hypoxia (air at 380 mm Hg). In nontransgenic but not in elafin-transgenic mice, we documented a transient increase in serine Elastase activity after 12 hours of hypoxic exposure attributed to a 30-kDa protein as determined by elastin zymography and fluorophosphonate/fluorophosphate-biotin labeling. Two...
-
arterial Elastase activity after balloon angioplasty and effects of elafin an Elastase Inhibitor
Arteriosclerosis Thrombosis and Vascular Biology, 2001Co-Authors: Alan W Barolet, Marlene Rabinovitch, Nafiseh Nili, Asim N Cheema, Ranga Robinson, Madhu K Natarajan, Stacy B Oblenes, Mohammad R Eskandarian, John D Sparkes, Bradley H StraussAbstract:Increased proteolytic activity may be a factor in intimal hyperplasia after balloon angioplasty (BA). The objectives of this study were to assess Elastase activity after BA in a rabbit arterial double-injury model and the effects of Elastase inhibition. Elastase activity increased immediately after BA, reached an 8-fold peak at 1 week, and declined to baseline levels by 4 weeks. Elastin zymography showed that the Elastase activity was associated predominantly with a molecular mass of 25 kDa. Elastase activity was significantly inhibited in vitro by elafin and phenylmethylsulfonyl fluoride, selective Inhibitors of serine Elastases. A second group of animals was transfected after BA with a plasmid containing the cDNA for either elafin or a control (chloramphenicol acetyltransferase, CAT) construct by using a hemagglutinating virus of Japan–liposome transfection technique. Arterial segments were obtained at 48 hours, 1 week, and 4 weeks to assess transgene expression, arterial wall Elastase activity, and intimal cross-sectional area, respectively. Elafin transgene expression was evident at 48 hours and resulted in a significant (80%) inhibition of Elastase activity compared with chloramphenicol acetyltransferase–transfected arteries. There was a 43% reduction in intimal cross-sectional area in elafin-transfected arteries (0.28±0.22 versus 0.16±0.07 mm2 for CAT-transfected versus elafin-transfected arteries, respectively; P <0.05). These data suggest that an early increase in serine Elastase activity after BA contributes to intimal hyperplasia. Serine Elastase inhibition may be a potential therapeutic approach to inhibit intimal hyperplasia.
-
gene transfer of the serine Elastase Inhibitor elafin protects against vein graft degeneration
Circulation, 2000Co-Authors: Stacy B Oblenes, Syed H E Zaidi, Alexander Y L Cheah, Brendan A S Mcintyre, Yasufumi Kaneda, Marlene RabinovitchAbstract:Background—Leukocyte infiltration and serine Elastase activity lead to smooth muscle cell proliferation in association with posttransplant coronary arteriopathy and may also be involved in vein graft neointimal formation. A number of therapies have targeted cellular proliferation, but the inhibition of serine Elastase–mediated extracellular matrix remodeling has not been investigated as a potential strategy to prevent neointimal formation and subsequent atherosclerotic degeneration in vein grafts. Methods and Results—We studied jugular vein grafts 48 hours after interposition into the carotid arteries of rabbits and demonstrated inflammatory cell infiltration and elevated serine Elastase activity, a stimulus for matrix remodeling and deposition of elastin. Therefore, elastolytic activity in vein grafts was targeted through transient expression of the selective serine Elastase Inhibitor elafin with hemagglutinating virus of Japan liposome–mediated gene transfer. Elafin transfection reduced inflammation by ...
-
complete reversal of fatal pulmonary hypertension in rats by a serine Elastase Inhibitor
Nature Medicine, 2000Co-Authors: Kyle Northcote Cowan, Adrian Heilbut, Tilman Humpl, Marlene RabinovitchAbstract:Progression of pulmonary hypertension is associated with increased serine Elastase activity and the proteinase-dependent deposition of the extracellular matrix smooth muscle cell survival factor tenascin-C (refs. 1,2). Tenascin-C amplifies the response of smooth muscle cells to growth factors3, which are also liberated through matrix proteolysis4. Recent organ culture studies using hypertrophied rat pulmonary arteries have shown that Elastase Inhibitors suppress tenascin-C and induce smooth muscle cell apoptosis5,6. This initiates complete regression of the hypertrophied vessel wall by a coordinated loss of cellularity and extracellular matrix. We now report that Elastase Inhibitors can reverse advanced pulmonary vascular disease produced in rats by injecting monocrotaline, an endothelial toxin. We began oral administration of the peptidyl trifluoromethylketone serine Elastase Inhibitors M249314 or ZD0892 21 days after injection of monocrotaline. A 1-week treatment resulted in 92% survival, compared with 39% survival in untreated or vehicle-treated rats. Pulmonary artery pressure and muscularization were reduced by myocyte apoptosis and loss of extracellular matrix, specifically elastin and tenascin-C. After 2 weeks, pulmonary artery pressure and structure normalized, and survival was 86%, compared with 0% in untreated or vehicle-treated rats. Although concomitant treatment with various agents can reduce pulmonary hypertension7, we have documented complete regression after establishment of malignant monocrotaline-induced disease.
-
elafin a serine Elastase Inhibitor attenuates post cardiac transplant coronary arteriopathy and reduces myocardial necrosis in rabbits afer heterotopic cardiac transplantation
Journal of Clinical Investigation, 1996Co-Authors: B Cowan, O Baron, J Crack, C Coulber, G J Wilson, Marlene RabinovitchAbstract:We have related experimentally induced post-cardiac transplant coronary arteriopathy to increased elastolytic activity, IL-1beta, fibronectin-mediated inflammatory and smooth muscle cell (SMC) migration, and SMC proliferation. Since our in vitro studies show that a serine Elastase releases SMC mitogens and facilitates IL-lbeta induction of fibronectin, we hypothesized that administration in vivo of the specific serine Elastase Inhibitor, elafin, would decrease the post-cardiac transplant coronary arteriopathy. Cholesterol-fed rabbits underwent a heterotopic cardiac transplant without immunosuppression and received elafin (1.79 mg/kg per d continuous infusion after a 9 mg bolus, n = 6) or vehicle (n = 6). 1 wk later, hearts were harvested for morphometric, immunohistochemical, and biochemical analyses. A > 70% decrease in the total number of coronary arteries with intimal thickening in elafin-treated compared to control donor hearts (P < 0.002) was associated with reduced vascular elastolytic activity judged by fewer breaks in the internal elastic lamina (P < 0.03), less accumulation of immunoreactive fibronectin (P < 0.02), and reduced cell proliferation quantified by proliferating cell nuclear antigen (P < 0.0001). Despite myocardial lymphocytic infiltration, wet weight of elafin-treated donor hearts was reduced by 50% compared to untreated controls (P < 0.002) and associated with relative preservation of myocyte integrity, instead of extensive myocardial necrosis (P < 0.004). This protective effect correlated with decreased myocardial elastolytic activity (P < 0.0001) and inflammatory cell proliferation (P < 0.0001) and with an elafin-inhibitable Elastase in lymphocytes. Serine Elastase activity thus appears an important therapeutic target for post-cardiac transplant coronary arteriopathy and myocardial necrosis induced by rejection.
Helena Medenvrtovec - One of the best experts on this subject based on the ideXlab platform.
-
seminal Elastase Inhibitor complex a marker of genital tract inflammation and negative ivf outcome measures role for a silent inflammation
International Journal of Andrology, 2004Co-Authors: Branko Zorn, Alenka Sesekbriski, Irma Virantklun, Gaj Vidmar, M Kolbezen, Helena MedenvrtovecAbstract:Summary There is no consensus on whether and how male genital tract inflammation affects sperm fertilizing potential. The aims of this prospective study were to evaluate the Elastase-Inhibitor complex in seminal plasma (s-EI) level, a marker of male genital tract inflammation, in men undergoing in vitro fertilization (IVF) having no clinical signs of inflammation, and its association with semen characteristics, and the predictive role of s-EI for the outcome of IVF in terms of fertilization, embryo development to the blastocyst stage and pregnancy. The study involved 104 male partners of infertile couples with normal spermiogram undergoing IVF. On the day of oocyte retrieval, spermiogram and s-EI assessment using homogeneous immunoassay were performed. The outcome of IVF according to the s-EI level was assessed in 85 cycles with two or more oocytes. In 67 cycles embryos were cultured to the blastocyst stage. Spearman's and Pearson's correlation tests, chi-square test, and multiple linear and logistic regression analyses were used for statistical evaluation. Increased s-EI level (≥250 μg/L) was detected in semen of 32% of men, and in 24% of men without leucocytospermia. We found an association between the s-EI level and semen leucocytes (r = 0.49, p = 0.004) but not with classical sperm characteristics. No correlation between the s-EI level and fertilization was observed. Increased s-EI levels were associated with a poorer blastocyst development rate (p = 0.03) and a higher number of arrested embryos (p = 0.04). Extended embryo culture to the blastocyst stage shows a negative effect of clinically silent male genital tract inflammation on embryo developmental potential.
-
semen granulocyte Elastase its relevance for the diagnosis and prognosis of silent genital tract inflammation
Human Reproduction, 2000Co-Authors: Branko Zorn, Irma Virantklun, Helena MedenvrtovecAbstract:Elastase-Inhibitor complex was assessed by immunoassay in the seminal plasma of 312 men attending the outpatient infertility clinic. Using receiver operating characteristic (ROC) curve analysis, Elastase at the cut-off value of > or =290 ng/ml was shown to be efficient (sensitivity 79.5%, specificity 74.4%) in the detection of genital tract inflammation as defined by leukocytospermia (>1x10(6) leukocytes/ml). The prevalence of increased Elastase in 292 infertile men was significantly higher (34%) as compared with that (5%) observed in 20 fertile men (P: = 0.02). Moreover, high Elastase concentration (> or =290 ng/ml) was observed in 66 of the 264 men (25%) without leukocytospermia. A significant positive correlation was found between Elastase concentration and patient age (r = 0.202, P: < 0.0001) and the number of leukocytes (r = 0.330, P: < 0.0001). A negative correlation was found between Elastase concentration and semen volume (r = -0.146, P: = 0.01) and the percentage of spermatozoa with single-stranded DNA (r = -0.194, P: = 0.024), but there was no correlation between Elastase and sperm reactive oxygen species production. A higher seminal Elastase concentration was significantly associated with tubal damage in female partners (P: < 0.001). After norfloxacine antibiotic therapy, decrease in Elastase concentration was observed in 15 (25%) of the 60 treated patients. Tubal damage in the partner negatively affected the response to antibiotic therapy. In conclusion, granulocyte Elastase is a reliable screening test for silent genital tract inflammation of the couple. The Elastase-Inhibitor complex may have a protective effect in reducing sperm DNA denaturation.