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

The late-phase allergic reaction (LPR) occurs 4 to 8 h after allergen exposure and probably causes the symptoms of chronic allergic disease. To determine the effects of soluble IL-1 receptor on the cutaneous LPR, we performed a prospective, randomized, double-blind, placebo-controlled study on 15 allergic subjects. Intradermal injections of allergen were placed on subjects' forearms, followed by immediate subcutaneous injections at the same site of either 1, 10, 25, 50, or 100 micrograms of rhu IL-1R to three subjects in each dosage group. Placebo was given to matched allergen-injected sites on the contralateral arm. Erythema, induration, and itching were recorded for each site. Sites were biopsied at 8 h for immunohistologic evaluations. Rhu IL-1R significantly reduced the clinical reaction at all concentrations. At 1 and 10 micrograms, measurements of LPR were significantly less (p < 0.05) than at placebo sites at several time points from 2 to 8 h. At higher concentrations, LPR was suppressed at rhu IL-1R and placebo sites, suggesting a systemic effect of rhu IL-1R. Histologic evaluation and indirect immunofluorescence for eosinophil granule major basic protein, neutrophil elastase, and mast cell tryptase showed no statistical differences between rhu IL-1R and placebo sites or among doses. IL-1 plays an important role in the generation of allergic LPR. While microgram quantities of rhu IL-1R inhibited the clinical signs and symptoms of LPR, its effects on the allergic inflammatory infiltrate are yet to be defined. In this short term trial, rhu IL-1R was neither immunogenic nor toxic.
 ...
PMID:Human cutaneous allergic late-phase response is inhibited by soluble IL-1 receptor. 812 Apr 5

We present the first direct biochemical evidence for the turnover of intact type VI collagen microfibrils. Matrix-degrading enzymes of the serine proteinase class, including rat mast cell chymases I and II, human mast cell tryptase, neutrophil elastase, cathepsin G and trypsin, were able to catabolize intact type VI collagen microfibrils isolated from foetal bovine skin and metabolically labelled intact type VI collagen immunoprecipitated from fibroblast culture medium. By contrast, intact type VI collagen was not degraded by the human matrix metalloproteinases, MMP-1, MMP-2, MMP-3 and MMP-9. These data have important implications for the stability of type VI collagen in connective tissues and highlight the potential role of serine proteinases both in normal type VI collagen turnover and in inflammatory conditions characterized by matrix degradation.
 ...
PMID:Catabolism of intact type VI collagen microfibrils: susceptibility to degradation by serine proteinases. 846

Toluene diisocyanate (TDI) is the most prevalent agent in occupational asthma (OA) in Korea. The immuno-pathologic mechanism for TDI-induced bronchoconstriction remains to be clarified. We studied the immunohistochemical finding of inflammatory cells in bronchial mucosa in subjects with TDI-induced asthma. Fiberoptic bronchial biopsy specimens were obtained from nine subjects with TDI-induced asthma. Six allergic asthma sensitive to house dust mite were enrolled as controls. Bronchial biopsy specimens were examined by immunohistology with a panel of monoclonal antibodies to mast cell tryptase (AA1), secretary form of eosinophil cationic protein (EG2), pan T-lymphocyte (CD3) and neutrophil elastase (NE). There was a significant increase in the number of AA1+, EG2+ and NE+ cells in TDI-induced asthma compared to those of allergic asthma (p=0.02, p=0.04, p=0.03, respectively). No significant differences were observed in the number of CD3+ cells (p=0.27). These findings support the view that neutrophil recruitment together with eosinophil and mast cell, may contribute to the bronchoconstriction induced by TDI.
 ...
PMID:Immunohistochemical characterization of the cellular infiltrate in airway mucosa of toluene diisocyanate (TDI)-induced asthma: comparison with allergic asthma. 953 14

Coprocessing of kininogens by a mixture of human mast cell tryptase and neutrophil elastase was explored as a potential substitute for the kallikrein-dependent pathway for kinin generation during inflammation. Tryptase easily excised bradykinin from the synthetic heptadecapeptide, ISLMKRPPGFSPFRSSR, but was unable to produce significant amounts of kinin by proteolysis of kininogens. However, a mixture of tryptase and elastase released bradykinin from each protein with a yield comparable to that of human plasma kallikrein. Significantly, neither plasma nor tissue kallikrein was able to effectively process N-chlorosuccinimide-oxidized high molecular weight kininogen, an effect attributed to the oxidation of a methionine residue upstream from the N terminus of the kinin domain. In support of these results the model heptadecapetide, ISL(MO)KRPPGFSPFRSSR, was also resistant to hydrolysis by either kallikrein. In contrast, the release of bradykinin from oxidized peptide or protein substrates by the tryptase/elastase mixture was not altered. Because kininogen modification may occur at inflammatory sites, as a result of the oxidative burst of recruited neutrophils and macrophages, these results suggest an alternative pathway for kinin production and the necessity for the novel utilization of two specific proteinases known to be released from these cells during inflammatory episodes.
 ...
PMID:A novel mechanism for bradykinin production at inflammatory sites. Diverse effects of a mixture of neutrophil elastase and mast cell tryptase versus tissue and plasma kallikreins on native and oxidized kininogens. 983 92

Polymorphic eruption of pregnancy (PEP) and herpes gestationis (HG) are pregnancy-related dermatoses of unknown aetiology with eosinophil infiltration which, at early stages, may show similar clinical and histopathological features. To determine the relative contributions of eosinophils, neutrophils and mast cells to the pathogenesis of PEP and HG through deposition of granule proteins, we studied tissue and serum from 15 patients with PEP and 10 with HG. Using indirect immunofluorescence with antibodies to human eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), neutrophil elastase and mast cell tryptase, we determined and compared cellular and extracellular staining patterns in lesional skin biopsy specimens and, using immunoassay, measured MBP, EDN, and ECP in patients' sera. Eosinophil infiltration and extracellular protein deposition of all three eosinophil granule proteins were present in both PEP and HG indicating a pathogenic role for eosinophils in both diseases. Staining for eosinophil granule proteins was especially prominent in urticarial lesions and around blisters in HG. EDN and ECP serum levels in PEP and ECP serum levels in HG were significantly increased compared with those in normal pregnant and normal nonpregnant serum. Neutrophils were more prominent in HG specimens than in PEP specimens; extracellular neutrophil elastase was minimally present and similar in both diseases. Mast cell numbers and extracellular tryptase deposition did not differ between the two diseases and did not differ from mast cell counts in skin of normal pregnant women. This study shows that eosinophil granule proteins are deposited extracellularly in tissue and are increased in serum in both PEP and HG. Moreover, eosinophil involvement in the two diseases is more consistent than neutrophil and mast cell involvement. Comparatively, tissue eosinophil infiltration and extracellular protein deposition is more extensive in HG than in PEP, suggesting that eosinophil involvement is greater in the pathogenesis of HG than PEP and similar to that found in bullous pemphigoid.
 ...
PMID:Polymorphic eruption of pregnancy and herpes gestationis: comparison of granulated cell proteins in tissue and serum. 1035 84

The endometrium undergoes edematous changes during the implantation period. Many factors may be involved in these biochemical reactions. We investigated the localization of inducible NO synthase (iNOS), interleukin-8 (IL-8), mast cell tryptase, neutrophil elastase, type III collagen, and CD44 in human endometrium. Immunohistochemical staining was performed by the labeled streptavidin-biotin method. iNOS was stained in the entire endometrial tissue from the midproliferative phase. The IL-8-positive cells, mast cells, and neutrophil elastase in the stroma increased toward the early to midsecretory phase. Type III collagen was arranged regularly in the stromal extracellular matrix during the proliferative phase; however, it was dissected during the secretory phase. CD44 was detected around stromal cells in the midsecretory phase. From these results, we propose the following mechanism. Initially, iNOS, expressed by the entire endometrial tissues from the midproliferative phase, catalyzes the production of NO. NO stimulates cells, supposed to be mast cells, to produce IL-8, which lets neutrophils migrate into the stroma. Neutrophils secrete elastase, which degrades type III collagen, generating spaces in the stroma. Hyaluronic acid adheres to CD44 around the stromal cells and retains water intermolecularly, finally forming the edematous matrix.
 ...
PMID:Studies on the mechanism of edematous changes at the endometrial stroma for implantation. 1137 73

Leukocytes and lung structural cells contribute to the pathophysiology of asthma through the production of numerous mediators including serine proteases. Such proteases include mast cell tryptase and chymase; neutrophil elastase, cathepsin G and myeloblastin (proteinase 3); bronchial epithelial cell-derived transmembrane protease, serine 11D (human airway trypsin-like protease); cytotoxic T lymphocyte- and natural killer cell-derived granzyme B; and, eosinophil serine protease 1 (testisin). Considerable effort to develop potent and selective inhibitors, mostly non-peptidic, especially targeting tryptase and chymase have been made in the last few years. This review presents promising inhibitors, currently in the research and development pipeline. Some endogenous inhibitors and other compounds purified from non-human species are also discussed.
 ...
PMID:Targeting serine proteases in asthma. 1661 Nov 50

hDDPI (human dipeptidyl peptidase I) is a lysosomal cysteine protease involved in zymogen activation of granule-associated proteases, including granzymes A and B from cytotoxic T-lymphocytes and natural killer cells, cathepsin G and neutrophil elastase, and mast cell tryptase and chymase. In the present paper, we provide the first crystal structure of an hDPPI-inhibitor complex. The inhibitor Gly-Phe-CHN2 (Gly-Phe-diazomethane) was co-crystallized with hDPPI and the structure was determined at 2.0 A (1 A=0.1 nm) resolution. The structure of the native enzyme was also determined to 2.05 A resolution to resolve apparent discrepancies between the complex structure and the previously published structure of the native enzyme. The new structure of the native enzyme is, within the experimental error, identical with the structure of the enzyme-inhibitor complex presented here. The inhibitor interacts with three subunits of hDPPI, and is covalently bound to Cys234 at the active site. The interaction between the totally conserved Asp1 of hDPPI and the ammonium group of the inhibitor forms an essential interaction that mimics enzyme-substrate interactions. The structure of the inhibitor complex provides an explanation of the substrate specificity of hDPPI, and gives a background for the design of new inhibitors.
 ...
PMID:The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2. 1702 May 38

Respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are a major health burden on society and current treatment modalities for these diseases have not significantly changed over the past 40 years. The only major pharmacological advancement for the treatment of these diseases has been to increase the duration of action of bronchodilators (asthma: salmeterol; COPD: tiotropium bromide) and glucocorticosteroids (asthma: fluticasone propionate) and, increasingly, to formulate these agents in the same delivery device. Despite our increasing understanding of the cell and molecular biology of these diseases, the development of novel treatments remains beyond the reach of the scientific community. Proteases are a family of proteins with diverse biological activity, which are found in abundance within the airways of asthma and COPD, and have been implicated in the pathogenesis of these diseases. The targeting of proteases, including mast cell tryptase, neutrophil elastase and matrix metalloprotease with low-molecular-weight inhibitors, has highlighted the potential role of these enzymes in mediating certain aspects of the disease process in preclinical studies. Several challenges remain regarding the development of protease inhibitors, including the synthesis of highly potent and specific inhibitors, and target validation in man.
 ...
PMID:Protease inhibitors in respiratory disease: focus on asthma and chronic obstructive pulmonary disease. 2047 80

The aim of this study was to evaluate the histological characteristics of the myometrium obtained in postpartum hemorrhage (PPH) of unknown etiology secondary to uterine atony. These characteristics were selected from among registered cases of clinically suspected amniotic fluid embolism (AFE) and classified as PPH of unknown etiology because of no obvious cause of PPH at Hamamatsu University School of Medicine, a registration center for clinical AFE in Japan. Immunohistochemical studies were performed on myometrium using anti-mast cell tryptase, anti-neutrophil elastase, anti-CD68, anti-CD88, anti-CD3, and anti-ZnCP-1 antibodies. Massive infiltrations of inflammatory cells with mast cell degranulation within the myometrium secondary to complement activation were observed in PPH of unknown etiology (n=34), but not in control pregnant women (n=15) or after delivery in women without PPH (n=18). The concomitant immunohistochemical detection of meconium in myometrium suggests that amniotic fluids or fetal materials are one of the candidates for inducing maternal local immune activation in the PPH of unknown etiology. Postpartum acute myometritis in the absence of an infective etiology may be a histological characteristic of PPH of unknown etiology.
...
PMID:Histological characteristics of the myometrium in the postpartum hemorrhage of unknown etiology: a possible involvement of local immune reactions. 2604 52


1 2 Next >>