80 results found
Mincham KT, Bruno N, Singanayagam A, et al., 2021, Our evolving view of neutrophils in defining the pathology of chronic lung disease, IMMUNOLOGY, Vol: 164, Pages: 701-721, ISSN: 0019-2805
Kobold N, Dekkak B, Flajolet P, et al., 2020, Characterisation of type two immune responses in a murine model of allergic airway disease, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Harker JA, Snelgrove RJ, 2020, A Not-So-Good Way to Die? Respiratory Syncytial Virus-induced Necroptotic Cell Death Promotes Inflammation and Type 2-mediated Pathology, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 201, Pages: 1321-1323, ISSN: 1073-449X
Turnbull A, Pyle C, Patel D, et al., 2020, Abnormal pro-gly-pro pathway and airway neutrophilia in pediatric cystic fibrosis, Journal of Cystic Fibrosis, Vol: 19, Pages: 40-48, ISSN: 1569-1993
BackgroundProline–glycine–proline (PGP) is a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP-9) and prolylendopeptidase (PE), and capable of eliciting neutrophil chemotaxis and epithelial remodelling. PGP is normally then degraded by leukotriene A4 hydrolase (LTA4H) to limit inflammation and remodelling. This study hypothesized that early and persistent airway neutrophilia in Cystic Fibrosis (CF) may relate to abnormalities in the PGP pathway and sought to understand underlying mechanisms.MethodsBroncho-alveolar lavage (BAL) fluid was obtained from 38 CF (9 newborns and 29 older children) and 24 non-CF children. BAL cell differentials and levels of PGP, MMP-9, PE and LTA4H were assessed.ResultsWhilst PGP was present in all but one of the older CF children tested, it was absent in non-CF controls and the vast majority of CF newborns. BAL levels of MMP-9 and PE were elevated in older children with CF relative to CF newborns and non-CF controls, correlating with airway neutrophilia and supportive of PGP generation. Furthermore, despite extracellular LTA4H commonly being greatly elevated concomitantly with inflammation to promote PGP degradation, this was not the case in CF children, potentially owing to degradation by neutrophil elastase.ConclusionsA striking imbalance between PGP-generating and -degrading enzymes enables PGP accumulation in CF children from early life and potentially supports airway neutrophilia.
Patel DF, Peiro T, Bruno N, et al., 2019, Neutrophils restrain allergic airway inflammation by limiting ILC2 function and monocyte-dendritic cell antigen presentation, Science Immunology, Vol: 4, Pages: 1-18, ISSN: 2470-9468
Neutrophil mobilization, recruitmentand clearancemust be tightly regulated asover-exuberant neutrophilic inflammation isimplicated in the pathology of chronic diseases, including asthma. Efforts to target neutrophilstherapeutically have failed to consider theirpleiotropic functions and theimplications of disrupting fundamental regulatory pathways that govern their turnover duringhomeostasisand inflammation.Using thehouse dust mite(HDM)model of allergic airways disease, we demonstrate that neutrophil depletion unexpectedly resulted in exacerbated TH2 inflammation, epithelial remodelling and airway resistance. Mechanistically, this was attributable to astriking increase insystemic G-CSF concentrations, which are ordinarily negatively regulated in the periphery by transmigrated lung neutrophils. Intriguingly, we found that increasedG-CSF augmented allergic sensitization in HDM exposed animals bydirectly acting on airway ILC2s toelicitcytokine production.Moreover, increased systemic G-CSF promoted expansion of bone marrow monocyte progenitor populations, which resulted in enhanced antigen presentation by an augmented peripheral monocyte-derived dendritic cell pool.By modelling the effects of neutrophil depletion, our studies have therefore uncovered previously unappreciated roles for G-CSF in modulating ILC2 function and antigen presentation. More broadly,they highlight an unexpected regulatory role for neutrophils in limiting TH2 allergic airway inflammation.
Singanayagam A, Snelgrove RJ, 2019, Less burn, more fat: electronic cigarettes and pulmonary lipid homeostasis, JOURNAL OF CLINICAL INVESTIGATION, Vol: 129, Pages: 4077-4079, ISSN: 0021-9738
Salek-Ardakani S, Bell T, Jagger CP, et al., 2019, CD200R1 regulates eosinophilia during pulmonary fungal infection in mice, EUROPEAN JOURNAL OF IMMUNOLOGY, ISSN: 0014-2980
Snelgrove RJ, Patel DF, 2019, Zooming into the Matrix: Using Nonlinear Optical Microscopy to Visualize Collagen Remodeling in Asthmatic Airways, American Journal of Respiratory and Critical Care Medicine, Vol: 200, Pages: 403-413, ISSN: 1073-449X
Bell TJ, Brand OJ, Morgan DJ, et al., 2019, Defective lung function following influenza virus is due to prolonged, reversible hyaluronan synthesis, MATRIX BIOLOGY, Vol: 80, Pages: 14-28, ISSN: 0945-053X
Patel DF, Gaggar A, Blalock JE, et al., 2019, Response to Comment on "An extracellular matrix fragment drives epithelial remodeling and airway hyperresponsiveness", SCIENCE TRANSLATIONAL MEDICINE, Vol: 11, ISSN: 1946-6234
Dean CH, Snelgrove RJ, 2018, New rules for club development: new insights into human small airway epithelial club cell ontogeny and function, American Journal of Respiratory and Critical Care Medicine, Vol: 198, Pages: 1355-1366, ISSN: 1073-449X
Snelgrove RJ, Patel DF, Patel T, et al., 2018, The enigmatic role of the neutrophil in asthma: Friend, foe or indifferent?, Clinical and Experimental Allergy, Vol: 48, Pages: 1275-1285, ISSN: 0954-7894
Whilst severe asthma has classically been categorized as a predominantly Th2-driven pathology, there has in recent years been a paradigm shift with the realization that it is a heterogeneous disease that may manifest with quite disparate underlying inflammatory and remodelling profiles. A subset of asthmatics, particularly those with a severe, corticosteroid refractory disease, present with a prominent neutrophilic component. Given the potential of neutrophils to impart extensive tissue damage and promote inflammation, it has been anticipated that these cells are closely implicated in the underlying pathophysiology of severe asthma. However, uncertainty persists as to why the neutrophil is present in the asthmatic lung and what precisely it is doing there, with evidence supporting its role as a protagonist of pathology being primarily circumstantial. Furthermore, our view of the neutrophil as a primitive, indiscriminate killer has evolved with the realization that neutrophils can exhibit a marked anti-inflammatory, pro-resolving and wound healing capacity. We suggest that the neutrophil likely exhibits pleiotropic and potentially conflicting roles in defining asthma pathophysiology-some almost certainly detrimental and some potentially beneficial-with context, timing and location all critical confounders. Accordingly, indiscriminate blockade of neutrophils with a broad sword approach is unlikely to be the answer, but rather we should first seek to understand their complex and multifaceted roles in the disease state and then target them with the same subtleties and specificity that they themselves exhibit.
Patel D, Peiro T, Shoemark A, et al., 2018, An extracellular matrix fragment drives epithelial remodeling and airway hyper-responsiveness, Science Translational Medicine, Vol: 10, Pages: 1-13, ISSN: 1946-6234
It is anticipated that bioactive fragments of the extracellular matrix (matrikines) can influence the development and progression of chronic diseases. The enzyme leukotriene A4 hydrolase (LTA4H) mediates opposing proinflammatory and anti-inflammatory activities, through the generation of leukotriene B4 (LTB4) and degradation of proneutrophilic matrikine Pro-Gly-Pro (PGP), respectively. We show that abrogation of LTB4 signaling ameliorated inflammation and airway hyperresponsiveness (AHR) in a murine asthma model, yet global loss of LTA4H exacerbated AHR, despite the absence of LTB4. This exacerbated AHR was attributable to a neutrophil-independent capacity of PGP to promote pathological airway epithelial remodeling. Thus, we demonstrate a disconnect between airway inflammation and AHR and the ability of a matrikine to promote an epithelial remodeling phenotype that negatively affects lung function. Subsequently, we show that substantial quantities of PGP are detectable in the sputum of moderate-severe asthmatics in two distinct cohorts of patients. These studies have implications for our understanding of remodeling phenotypes in asthma and may rationalize the failure of LTA4H inhibitors in the clinic.
Snelgrove RJ, Lloyd CM, 2018, Tasting type 2 inflammation in the airways, Journal of Allergy and Clinical Immunology, Vol: 142, Pages: 403-404, ISSN: 0091-6749
Lloyd CM, Snelgrove RJ, 2018, Type 2 immunity: expanding our view., Science Immunology, Vol: 3, ISSN: 2470-9468
The classical vision of type 2 immune reactions is that they are characterized by a distinct cellular and cytokine repertoire that is critical for host resistance against helminthic worm infections but, when dysregulated, may cause atopic reactions that result in conditions such as asthma, rhinitis, dermatitis, and anaphylaxis. In this traditional view, the type 2 response is categorized as an adaptive immune response with differentiated T helper cells taking center stage, driving eosinophil recruitment and immunoglobulin production via the secretion of a distinct repertoire of cytokines that include interleukin-4 (IL-4), IL-5, and IL-13. The recent discovery of a group of innate cells that has the capacity to secrete copious amounts of type 2 cytokines, potentially in the absence of adaptive immunity, has reignited interest in type 2 biology. The discovery that these innate lymphoid cells and type 2 cytokines are involved in diverse biological processes-including wound healing, control of metabolic homeostasis, and temperature-has considerably changed our view of type 2 responses and the cytokines, chemokines, and receptors that regulate these responses.
Patel DF, Snelgrove RJ, 2018, The multifaceted roles of the matrikine Pro-Gly-Pro in pulmonary health and disease, European Respiratory Review, Vol: 27, ISSN: 0905-9180
Matrikines are bioactive fragments of the extracellular matrix (ECM) that are fundamental in regulating a diverse array of physiological processes. The tripeptide Proline-Glycine-Proline (PGP) is a collagen-derived matrikine that has classically been described as a neutrophil chemoattractant. In this article, we describe our current understanding of the pathways that generate, degrade and modify PGP to dictate its bioavailability and stability. Additionally, we discuss our expanding appreciation of the capacity of PGP to regulate diverse cell types and biological processes, independent of its activity on neutrophils, including a putative role in wound repair. We argue that PGP functions as a primitive and conserved damage-associated molecular pattern, which is generated during infection or injury and subsequently acts to shape ensuing inflammatory and repair processes. As a fragment of the ECM that accumulates at the epicentre of the action, PGP is perfectly positioned to focus neutrophils to the exact site required and direct a localised repair response. However, it is essential that PGP is efficiently degraded, as if this matrikine is allowed to persist then pathology can ensue. Accordingly, we discuss how this pathway is subverted in chronic lung diseases giving rise to persistent inflammation and pathological tissue remodelling.
O'Reilly PJ, Ding Q, Akthar S, et al., 2017, Angiotensin-converting enzyme defines matrikine-regulated inflammation and fibrosis, JCI INSIGHT, Vol: 2, ISSN: 2379-3708
The neutrophil chemoattractant proline-glycine-proline (PGP) is generated from collagen by matrix metalloproteinase-8/9 (MMP-8/9) and prolyl endopeptidase (PE), and it is concomitantly degraded by extracellular leukotriene A4 hydrolase (LTA4H) to limit neutrophilia. Components of cigarette smoke can acetylate PGP, yielding a species (AcPGP) that is resistant to LTA4H-mediated degradation and can, thus, support a sustained neutrophilia. In this study, we sought to elucidate if an antiinflammatory system existed to degrade AcPGP that is analogous to the PGP-LTA4H axis. We demonstrate that AcPGP is degraded through a previously unidentified action of the enzyme angiotensin-converting enzyme (ACE). Pulmonary ACE is elevated during episodes of acute inflammation, as a consequence of enhanced vascular permeability, to ensure the efficient degradation of AcPGP. Conversely, we suggest that this pathway is aberrant in chronic obstructive pulmonary disease (COPD) enabling the accumulation of AcPGP. Consequently, we identify a potentially novel protective role for AcPGP in limiting pulmonary fibrosis and suggest the pathogenic function attributed to ACE in idiopathic pulmonary fibrosis (IPF) to be a consequence of overzealous AcPGP degradation. Thus, AcPGP seemingly has very divergent roles: it is pathogenic in its capacity to drive neutrophilic inflammation and matrix degradation in the context of COPD, but it is protective in its capacity to limit fibrosis in IPF.
Peiró T, Patel DF, Akthar S, et al., 2017, Neutrophils drive alveolar macrophage IL-1β release during respiratory viral infection, Thorax, Vol: 73, Pages: 546-556, ISSN: 1468-3296
Background Alveolar macrophages are sentinels of the airways that must exhibit immune restraint to innocuous antigens but elicit a robust inflammatory response to pathogenic threats. How distinction between these dichotomous functions is controlled is poorly defined.Neutrophils are the first responders to infection, and we hypothesised that they may free alveolar macrophages from their hyporesponsive state, promoting their activation. Activation of the inflammasome and interleukin (IL)-1β release is a key early inflammatory event that must be tightly regulated. Thus, the role of neutrophils in defining inflammasome activation in the alveolar macrophage was assessed.Methods Mice were infected with the X31 strain of influenza virus and the role of neutrophils in alveolar macrophage activation established through administration of a neutrophil-depleting (1A8) antibody.Results Influenza elicited a robust IL-1β release that correlated (r=0.6849; p<0.001) with neutrophil infiltrate and was ablated by neutrophil depletion. Alveolar macrophages were shown to be the prominent source of IL-1β during influenza infection, and virus triggered the expression of Nod-like receptor protein 3 (NLRP3) inflammasome and pro-IL-1β in these cells. However, subsequent activation of the inflammasome complex and release of mature IL-1β from alveolar macrophages were critically dependent on the provision of a secondary signal, in the form of antimicrobial peptide mCRAMP, from infiltrating neutrophils.Conclusions Neutrophils are critical for the activation of the NLRP3 inflammasome in alveolar macrophages during respiratory viral infection. Accordingly, we rationalise that neutrophils are recruited to the lung to confront a viable pathogenic threat and subsequently commit alveolar macrophages to a pro-inflammatory phenotype to combat infection.
Snelgrove RJ, Lloyd CM, 2017, An NLRP3, IL-1 beta, Neutrophil Axis in the Respiratory Tract Leaves You Breathless, American Journal of Respiratory and Critical Care Medicine, Vol: 196, Pages: 253-254, ISSN: 1073-449X
Baker K, Raemdonck K, Snelgrove RJ, et al., 2017, Characterisation of a murine model of the late asthmatic response, Respiratory Research, Vol: 18, ISSN: 1465-9921
Background: The incidence of asthma is increasing at an alarming rate. While the current available therapies areeffective, there are associated side effects and they fail to adequately control symptoms in all patient subsets. In thesearch to understand disease pathogenesis and find effective therapies hypotheses are often tested in animalmodels before progressing into clinical studies. However, current dogma is that animal model data is often notpredictive of clinical outcome. One possible reason for this is the end points measured such as antigen-challengeinduced late asthmatic response (LAR) is often used in early clinical development, but seldom in animal modelsystems. As the mouse is typically selected as preferred species for pre-clinical models, we wanted to characteriseand probe the validity of a murine model exhibiting an allergen induced LAR.Methods: C57BL/6 mice were sensitised with antigen and subsequently topically challenged with the sameantigen. The role of AlumTM adjuvant, glucocorticoid, long acting muscarinic receptor antagonist (LAMA), TRPA1,CD4+ and CD8+ T cells, B cells, Mast cells and IgE were determined in the LAR using genetically modified mice anda range of pharmacological tools.Results: Our data showed that unlike other features of asthma (e.g. cellular inflammation, elevated IgE levels andairway hyper-reactivity (AHR) the LAR required AlumTMadjuvant. Furthermore, the LAR appeared to be sensitive toglucocorticoid and required CD4+ T cells. Unlike in other species studied, the LAR was not sensitive to LAMAtreatment nor required the TRPA1 ion channel, suggesting that airway sensory nerves are not involved in the LARin this species. Furthermore, the data suggested that CD8+ T cells and the mast cell—B-cell - IgE axis appear to beprotective in this murine model.Conclusion: Together we can conclude that this model does feature steroid sensitive, CD4+ T cell dependent,allergen induced LAR. However, collectively our data questions the validit
Low CM, Akthar S, Patel D, et al., 2017, The development of novel LTA4H modulators to selectively target LTB4 generation, Scientific Reports, Vol: 7, ISSN: 2045-2322
The pro-inflammatory mediator leukotriene B4 (LTB4) is implicated in the pathologies of an array of diseases and thus represents an attractive therapeutic target. The enzyme leukotriene A4 hydrolase (LTA4H) catalyses the distal step in LTB4 synthesis and hence inhibitors of this enzyme have been actively pursued. Despite potent LTA4H inhibitors entering clinical trials all have failed to show efficacy. We recently identified a secondary anti-inflammatory role for LTA4H in degrading the neutrophil chemoattractant Pro-Gly-Pro (PGP) and rationalized that the failure of conventional LTA4H inhibitors may be that they inadvertently prevented PGP degradation. We demonstrate that these inhibitors do indeed fail to discriminate between the dual activities of LTA4H, and enable PGP accumulation in mice. Accordingly, we have developed novel compounds that potently inhibit LTB4 generation whilst leaving PGP degradation unperturbed. These novel compounds could represent a safer and superior class of LTA4H inhibitors for translation into the clinic.
Weiss G, Lai C, Fife ME, et al., 2016, Reversal of TREM-1 ectodomain shedding and improved bacterial clearance by intranasal metalloproteinase inhibitors, MUCOSAL IMMUNOLOGY, Vol: 10, Pages: 1021-1030, ISSN: 1933-0219
Baker K, Raemdonck K, Dekkak B, et al., 2016, Role of the ion channel, transient receptor potential cation channel subfamily V member 1 (TRPV1), in allergic asthma, Respiratory Research, Vol: 17, ISSN: 1465-993X
BACKGROUND: Asthma prevalence has increased world-wide especially in children; thus there is a need to develop new therapies that are safe and effective especially for patients with severe/refractory asthma. CD4(+) T cells are thought to play a central role in disease pathogenesis and associated symptoms. Recently, TRPV1 has been demonstrated to regulate the activation and inflammatory properties of CD4(+) cells. The aim of these experiments was to demonstrate the importance of CD4(+) T cells and the role of TRPV1 in an asthma model using a clinically ready TRPV1 inhibitor (XEN-D0501) and genetically modified (GM) animals. METHODS: Mice (wild type, CD4 (-/-) or TRPV1 (-/-)) and rats were sensitised with antigen (HDM or OVA) and subsequently topically challenged with the same antigen. Key features associated with an allergic asthma type phenotype were measured: lung function (airway hyperreactivity [AHR] and late asthmatic response [LAR]), allergic status (IgE levels) and airway inflammation. RESULTS: CD4(+) T cells play a central role in both disease model systems with all the asthma-like features attenuated. Targeting TRPV1 using either GM mice or a pharmacological inhibitor tended to decrease IgE levels, airway inflammation and lung function changes. CONCLUSION: Our data suggests the involvement of TRPV1 in allergic asthma and thus we feel this target merits further investigation.
Snelgrove RJ, 2015, Matrikines are key regulators in modulating the amplitude of lung inflammation in acute pulmonary infection, Nature Communications, Vol: 6, Pages: 1-14, ISSN: 2041-1723
Bioactive matrix fragments (matrikines) have been identified in a myriad of disorders, but their impact on the evolution of airway inflammation has not been demonstrated. We recently described a pathway where the matrikine and neutrophil chemoattractant proline–glycine–proline (PGP) could be degraded by the enzyme leukotriene A4 hydrolase (LTA4H). LTA4H classically functions in the generation of pro-inflammatory leukotriene B4, thus LTA4H exhibits opposing pro- and anti-inflammatory activities. The physiological significance of this secondary anti-inflammatory activity remains unknown. Here we show, using readily resolving pulmonary inflammation models, that loss of this secondary activity leads to more pronounced and sustained inflammation and illness owing to PGP accumulation. PGP elicits an exacerbated neutrophilic inflammation and protease imbalance that further degrades the extracellular matrix, generating fragments that perpetuate inflammation. This highlights a critical role for the secondary anti-inflammatory activity of LTA4H and thus has consequences for the generation of global LTA4H inhibitors currently being developed.
Castanhinha S, Sherburn RT, Walker SA, et al., 2015, Pediatric severe asthma with fungal sensitization is mediated by steroid-resistant IL-33, Journal of Allergy and Clinical Immunology, Vol: 136, Pages: 312-322.e7, ISSN: 1097-6825
Background: The mechanism underlying severe asthma with fungal sensitization (SAFS) is unknown. IL-33 is important in fungus-induced asthma exacerbations, but its role in fungal sensitization is unexplored. Objective: We sought to determine whether fungal sensitization in children with severe therapy-resistant asthma is mediated by IL-33. Methods: Eighty-two children (median age, 11.7 years; 63% male) with severe therapy-resistant asthma were included. SAFS (n= 38) was defined as specific IgE or skin prick test response positivity to Aspergillus fumigatus, Alternaria alternata, or Cladosporium herbarum. Clinical features and airway immunopathology were assessed. Chronic exposure to house dust mite and A alternata were compared in a neonatal mouse model. Results: Children with SAFS had earlier symptom onset (0.5 vs 1.5 years, P= .006), higher total IgE levels (637 vs 177 IU/mL, P= .002), and nonfungal inhalant allergen-specific IgE. Significantly more children with SAFS were prescribed maintenance oral steroids (42% vs 14%, P= .02). SAFS was associated with higher airway IL-33 levels. In neonatal mice A alternata exposure induced higher serum IgE levels, pulmonary IL-33 levels, and IL-13+ innate lymphoid cell (ILC) and TH2 cell numbers but similar airway hyperresponsiveness (AHR) compared with those after house dust mite exposure. Lung IL-33 levels, IL-13+ ILC numbers, TH2 cell numbers, IL-13 levels, and AHR remained increased with inhaled budesonide during A alternata exposure, but all features were significantly reduced in ST2-/- mice lacking a functional receptor for IL-33. Conclusion: Pediatric SAFS was associated with more oral steroid therapy and higher IL-33 levels. A alternata exposure resulted in increased IL-33-mediated ILC2 numbers, TH2 cell numbers, and steroid-resistant AHR. IL-33 might be a novel therapeutic target for SAFS.
Sanders RD, Grover V, Goulding J, et al., 2015, Immune cell expression of GABA(A) receptors and the effects of diazepam on influenza infection, JOURNAL OF NEUROIMMUNOLOGY, Vol: 282, Pages: 97-103, ISSN: 0165-5728
Stack G, Jones E, Marsden M, et al., 2015, CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue, PLOS PATHOGENS, Vol: 11, ISSN: 1553-7366
Humphreys IR, Stacey MA, Marsden M, et al., 2014, Neutrophils recruited by IL-22 in peripheral tissues function as TRAIL-dependent antiviral effectors against MCMV, 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society (ICIS), Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, Pages: 48-49, ISSN: 1043-4666
Snelgrove RJ, Gregory LG, Peiro T, et al., 2014, Alternaria-derived serine protease activity drives IL-33-mediated asthma exacerbations, Journal of Allergy and Clinical Immunology, Vol: 134, Pages: 583-592.e6, ISSN: 1097-6825
BackgroundThe fungal allergen Alternaria alternata is implicated in severe asthma and rapid onset life-threatening exacerbations of disease. However, the mechanisms that underlie this severe pathogenicity remain unclear.ObjectiveWe sought to investigate the mechanism whereby Alternaria was capable of initiating severe, rapid onset allergic inflammation.MethodsIL-33 levels were quantified in wild-type and ST2−/− mice that lacked the IL-33 receptor given inhaled house dust mite, cat dander, or Alternaria, and the effect of inhibiting allergen-specific protease activities on IL-33 levels was assessed. An exacerbation model of allergic airway disease was established whereby mice were sensitized with house dust mite before subsequently being challenged with Alternaria (with or without serine protease activity), and inflammation, remodeling, and lung function assessed 24 hours later.ResultsAlternaria, but not other common aeroallergens, possessed intrinsic serine protease activity that elicited the rapid release of IL-33 into the airways of mice through a mechanism that was dependent upon the activation of protease activated receptor-2 and adenosine triphosphate signaling. The unique capacity of Alternaria to drive this early IL-33 release resulted in a greater pulmonary inflammation by 24 hours after challenge relative to the common aeroallergen house dust mite. Furthermore, this Alternaria serine protease–IL-33 axis triggered a rapid, augmented inflammation, mucus release, and loss of lung function in our exacerbation model.
Snelgrove R, Kheradmand F, 2014, Leukotriene A(4) Hydrolase: The Janus Enzyme Shows Its Ugly Side in Smokers, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 190, Pages: 5-7, ISSN: 1073-449X
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.