Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bovine respiratory syncytial virus (BRSV) infection is an important cause of outbreaks of respiratory disease among calves. This virus commonly induces mild to severe respiratory signs but, in a substantial proportion of cases, is also reported to be associated with paroxystic respiratory distress syndrome (PRDS). The pathogenesis of this 'malignant' clinical form has not been fully elucidated. The present study aimed at determining whether mast cell (MC) degranulation plays a role in the physiopathologic cascade leading to the PRDS. Paired serum samples were taken in herds during outbreaks of severe respiratory diseases (acute sera) and 3 weeks after (convalescent sera). Based on seroconversion to BRSV and clinical picture, 67 pairs of sera were selected from calves with a BRSV-associated PRDS for circulating MC tryptase determination. A MC metachromatic score was measured in post-mortem lungs from animals died from a BRSV-associated PRDS (principals) and compared with reference scores obtained from healthy lungs (controls). Levels of tryptase were significantly higher in acute sera (26.6 +/- 12.4 microg/l) compared to convalescent sera (8.4 +/- 7.8 microg/l; P<0.001). Metachromatic scores yielded significantly different results between controls and principals (P<0.01), demonstrating a significant disappearance of metachromatic granules from lung MCs in principals. Taken together, these data demonstrate the presence of an extensive MC degranulation in BRSV-associated PRDS.
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PMID:Extensive mast cell degranulation in bovine respiratory syncytial virus-associated paroxystic respiratory distress syndrome. 1474 Nov 32

We describe the history and lung pathology of a premature female infant, who presented with respiratory distress immediately after birth. A thoracic computerized tomography scan showed abnormalities suggestive of congenital cystic adenomatoid malformation of the left lung. In addition, echocardiography revealed a tetralogy of Fallot. A left thoracotomy was performed and the lower lobe of the left lung was removed. Despite intensive supportive therapy, pulmonary hypoperfusion resulted in severe hypoxemia and death. Gross and microscopic analysis of the resected lobe revealed a partly cystic and solid lesion with multiple bronchus-derived cysts and an exuberant multifocal proliferation of glandular tissue, resembling bronchial glands, mixed with heterotopic cartilage surrounding ducts. Immunohistochemical analysis showed the presence of chromogranin A-reactive islet-like structures amidst exocrine tissue showing trypsin and chymotrypsin immunoreactivity, establishing the diagnosis of pulmonary pancreatic heterotopy. In the remaining pulmonary parenchyma, there were secondary changes consistent with partial obstruction and lymphangiectasis which was attributed to the presence of the cardiac malformation. To our knowledge, this is only the fourth reported case of heterotopic pancreatic tissue in the lung, and the first case where this bronchopulmonary foregut anomaly is not associated with a enteric duplication.
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PMID:Heterotopic pancreatic tissue presenting as a solid and cystic lung lesion: a very unusual bronchopulmonary foregut malformation. 1517 63

Proteinase-activated receptor 2 (PAR(2)), a G-protein-coupled receptor activated by serine proteinases such as trypsin, has been suggested to play an important role in inflammatory and fibroproliferative processes. In preterm infants, the development of bronchopulmonary dysplasia (BPD) is characterized by early pulmonary inflammation and subsequent interstitial fibrosis. High pulmonary trypsin-2 has been shown to be associated with the development of BPD. We studied the expression and distribution of PAR(2) and trypsin-2 by immunohistochemistry in autopsy lung specimens of fetuses (n = 10), of preterm infants who died of acute or prolonged respiratory distress syndrome (RDS) (n = 8 and n = 7, respectively) or BPD (n = 6), and of newborn infants without lung disease (n = 5) who served as controls. In prolonged RDS and BPD, PAR(2) immunoreactivity was significantly higher in bronchial epithelium when compared with infants without pulmonary pathology (p < 0.05 and p < 0.005, respectively). In alveolar epithelium, expression of PAR(2) was elevated in prolonged RDS when compared with newborn infants without pulmonary pathology (p < 0.05). Moreover, strong expression of PAR(2) was detected in myofibroblasts of thickened and fibrotic alveolar walls in prolonged RDS or BPD. Trypsin-2 was co-localized with PAR(2) in bronchoalveolar epithelium. These findings suggest that PAR(2), possibly activated by trypsin-2, may participate in inflammation and fibroproliferation associated with progression of RDS toward BPD in preterm infants.
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PMID:High expression of pulmonary proteinase-activated receptor 2 in acute and chronic lung injury in preterm infants. 1587 99

Acute lung injury is marked by damage to alveolar-capillary barrier. High pulmonary levels of matrix-degrading serine proteinase trypsin and matrix metalloproteinases (MMP)-2, -8, and -9 have been shown in preterm infants with respiratory distress syndrome (RDS). We studied expression of trypsin and MMP-2, -8, and -9 in rats exposed to >95% oxygen for 24, 48, or 60 h. As demonstrated by zymography and Western immunoblotting, levels of trypsin and MMP-2, -8, and -9 in bronchoalveolar lavage fluid (BALF) sharply increased after 48 h of hyperoxia relative to normoxia controls. This coincided with increase in alveolar-capillary permeability, as indicated by increased protein concentration in BALF. Both neutrophil-derived 80-kD and mesenchymal cell-derived 60-kD MMP-8 isoforms were detected in BALF. Of them, mesenchymal-type MMP-8 predominated. In immunohistochemistry, alveolar epithelium showed strong trypsin expression at 48 and 60 h of hyperoxia, whereas it was predominantly negative in controls. MMP-8 was mostly expressed in macrophages. Marked up-regulation of trypsin and MMP-8 early during hyperoxic lung injury suggests that these enzymes play a role in the pathogenesis of acute lung injury and may therefore be potential targets for therapy of lung injury.
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PMID:Up-regulation of trypsin and mesenchymal MMP-8 during development of hyperoxic lung injury in the rat. 1694 Feb 37

Acute pancreatitis in its severe form is complicated by multiple organ system dysfunction, most importantly by pulmonary complications which include hypoxia, acute respiratory distress syndrome, atelectasis, and pleural effusion. The pathogenesis of some of the above complications is attributed to the production of noxious cytokines. Clinically significant is the early onset of pleural effusion, which heralds a poor outcome of acute pancreatitis. The role of circulating trypsin, phospholipase A2, platelet activating factor, release of free fatty acids, chemoattractants such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, IL-8, fMet-leu-phe (a bacterial wall product), nitric oxide, substance P, and macrophage inhibitor factor is currently studied. The hope is that future management of acute pancreatitis with a better understanding of the pathogenesis of lung injury will be directed against the production of noxious cytokines.
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PMID:Pathophysiology of pulmonary complications of acute pancreatitis. 1713 69

Protease activated receptors (PARs) are a small family of G protein-coupled receptors (GPCR) mediating the cellular effects of some proteases of the coagulation system, such as thrombin, or other proteases, such as trypsin or metalloproteinase 1. As the prototype of PARs, PAR1 is a seven transmembrane GPCR that, upon cleavage by thrombin, unmasks a new amino-terminus able to bind intramolecularly to PAR1 itself thus inducing signaling. In the vascular system, thrombin and other proteases of the coagulation-fibrinolysis system, such as plasmin, factor VIIa and factor Xa, activated protein C, are considered physiologically relevant agonists, and PARs appear to largely account for the cellular effects of these enzymes. In the vasculature, PARs are expressed on platelets, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). In the vessel wall, under physiological conditions, PARs are mainly expressed in ECs and participate in the regulation of vascular tone, by inducing endothelium-dependent relaxation. PAR activation on ECs promotes conversion of these cells into a proinflammatory phenotype, causes increase of vascular permeability, and the exposure/secretion of proteins and cytokines mediating the local accumulation of platelets and leukocytes. These effects contribute to the vascular consequences of sepsis and of diseases such as acute lung injury and acute respiratory distress syndrome. In normal arteries PARs are to a much lesser amount expressed on VSMCs. However, in conditions associated with endothelial dysfunction, PARs mediate contraction, proliferation, migration, hypertrophy of VSMCs and their production of extracellular matrix, thereby contributing to the pathophysiology of atherosclerosis and hypertension. Inhibition of protease-PAR interaction might thus become a potential therapeutic target in various vascular diseases.
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PMID:Functional role of protease activated receptors in vascular biology. 2492 9

Since its first appearance in December 2019 in the Chinese province of Wuhan, COVID-19 has spread rapidly throughout the world and poses a serious threat to public health. Acute respiratory failure due to widespread lung inflammation progress to acute respiratory distress syndrome (ARDS) with an altered pulmonary and alveolar function that can lead to disability, prolong hospitalizations, and adverse outcomes. While there is no specific treatment for severe acute lung injury (ALI) and ARDS due to the COVID-19 and the management is mostly supportive, it is very important to better understand the pathophysiological processes activated by the inflammatory mediators such as cytokines and metalloproteinases with the aim of their subsequent inhibition in the course of the complex treatment. Herein, we will discuss the pathophysiological mechanisms of ALI/ARDS, with a focus on the pivotal role played by matrix metalloproteinases (MMP) and the kinin-kallikrein system (KKS), and the effects of the possible pharmacological interventions. Aprotinin is a nonspecific protease inhibitor especially of trypsin, chymotrypsin, plasmin, and kallikrein, and it is many years in clinical use. Aprotinin inhibits the release of pro-inflammatory cytokines and involved in the process of glycoprotein homeostasis. Experimental data support that the use of aprotinin to inhibit MMPs and KKS may be a new potential approach to the treatment of ALI / ARDS.
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PMID:Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19. 3253 10


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