Oxidative regulation of neutrophil elastase-alpha-1-proteinase inhibitor interactions.

Ossanna, P J; Test, Samuel T.; Matheson, Nancy; Regiani, Sandra; Weiss, Stephen J.

doi:10.1172/jci112523

Cited by 183 publications

(102 citation statements)

References 75 publications

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“…Oxidation of the P1 methionine (methionine 358) or methionine 351 to methionine sulfoxide significantly reduces the ability of AAT to inhibit neutrophil elastase (Taggart et al, 2000). Hydrogen peroxide in cigarette smoke and N-chloroamines and hypochlorous acid in neutrophils can oxidize and inactivate AAT (Ossanna et al, 1986;Scott et al, 1999). Thus the oxidation of AAT by cigarette smoke or free radicals in vivo could lead to a relative deficiency of elastase inhibitors and has been suggested as a mechanism contributing to the development of emphysema and other diseases such as cystic fibrosis, adult respiratory distress syndrome, and bronchiectasis (McGuire et al, 1982;Roum et al, 1993;IzumiYoneda et al, 2009).…”

Section: Aatmentioning

confidence: 99%

Acute Phase Proteins: Structure and Function Relationship

Janciauskiene¹,

Welte²,

Mahadeva³

2011

Acute Phase Proteins - Regulation and Functions of Acute Phase Proteins

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Section: Aatmentioning

confidence: 99%

Acute Phase Proteins: Structure and Function Relationship

Janciauskiene¹,

Welte²,

Mahadeva³

2011

Acute Phase Proteins - Regulation and Functions of Acute Phase Proteins

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“…However, it is normally bound and at least partially inactivated by a 1 antitrypsin protease inhibitor. 13,14 The formed complex (elastase-a 1 -antitrypsin complex [E-a 1 -Pi]), which is stable and can easily be identified by an enzyme-linked immunoassay, has been shown to improve early diagnosis of neonatal septicemia. 15,16 It has also been found elevated in other inflammatory conditions, such as meningitis, inflammatory bowel disease, 17,18 etc.…”

mentioning

confidence: 99%

Polymorphonuclear Elastase as a Diagnostic Marker of Acute Pyelonephritis in Children

Fretzayas¹,

Moustaki²,

Gourgiotis³

et al. 2000

Pediatrics

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ABSTRACT. Objective. Experimental evidence suggests that neutrophils and their metabolites play an important role in the pathogenesis of pyelonephritis. The aim of this study was to investigate the diagnostic value of polymorphonuclear elastase-a 1 -antitrypsin complex (E-a 1 -Pi) for the detection of acute pyelonephritis in children.Methods. Eighty-three patients, 29 boys and 54 girls, 25 days to 14 years of age, with first-time symptomatic urinary tract infection were prospectively studied. Fiftyseven healthy children served as controls. Dimercaptosuccinic acid (DMSA) scan and voiding cystourethrography were performed in all patients. Plasma and urinary E-a 1 -Pi, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil count, urinary N-acetyl-␤-glucosaminidase (NAG), N-acetyl-␤-glucosaminidase b (NAG b), and creatinine levels were measured in all patients on admission and 3 days after the introduction of antibiotics. The same markers were also measured in the control subjects.Results. Planar DMSA scintigraphy demonstrated changes of acute pyelonephritis in 30 of 83 children (group A). It was normal in the remaining 53 children (group B). The sex and age distributions were not significantly different between the 2 groups, as well as between the patients and the control subjects (group C). Nineteen of the 53 children with a normal DMSA had body temperature >38°C, whereas all but 4 children with abnormal DMSA had temperature >38°C. Therefore, the temperature was significantly different between these 2 groups. The sensitivity and specificity of fever (>38°C) as an indicator of renal involvement based on isotopic findings were 86% and 64%, respectively. Given the significant number of the febrile children with normal DMSA scintiscans, group B was subdivided into B 1 with 19 febrile children (14 boys and 5 girls) and B 2 with 34 children whose body temperature was below 38°C (8 boys and 26 girls). The sex and age distribution was significantly different between groups B 1 and B 2 . The mean age of group B 1 was .78 years (range: 28 days to 9 years; median: .25 years; standard deviation: 2.1). All but 1 child in this group were younger than 1 year of age. In contrast, in group B 2 , there were only 4 infants, the remaining 30 children were older than 2.5 years (mean age: 6 years; median: 7 years; standard deviation: 3.5; range: 34 days to 12 years). The mean duration of fever before hospital admission was 2.8 days for group A and 1.8 days for group B 1 . This difference was not statistically significant. Similarly, body temperature was not significantly different between these 2 groups. The distribution of plasma E-a 1 -Pi values was normal in the control subjects. The sensitivity and specificity of plasma E-a 1 -Pi, as an indicator of renal involvement, were 96% and 50%, respectively, taking the 95th percentile of the reference range as a cutoff value. However, considering as a cutoff value the level of 72 g/dL (95th percentile of group B 2 ), its sensitivity and specificity were 74% and 86%, resp...

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“…Neutrophils that accumulate in the tissue secrete myeloperoxidase, which produces hydroxychloride (HOCl). HOCl has a direct cytotoxic effect and by inactivating a 1-protease inhibitor, it participates in the production of collagenases and elastases from the neutrophils [13,14]. The neutrophils in this environment favor the secretion of proinflammatory cytokines such as IL-6, IL-8, and TNF-α [14].…”

Section: Discussionmentioning

confidence: 99%