scholarly journals Interactions via α2β1 Cell Integrin May Protect against the Progression of Airway Structural Changes in Asthma

2021 ◽  
Vol 22 (12) ◽  
pp. 6315
Author(s):  
Stanislawa Bazan-Socha ◽  
Bogdan Jakiela ◽  
Joanna Zuk ◽  
Jacek Zarychta ◽  
Jerzy Soja ◽  
...  
Keyword(s):  
T Cells ◽  
Structural Changes ◽  
Type I Collagen ◽  
Airway Remodeling ◽  
Airflow Limitation ◽  
Type I ◽  
Asthma Patients ◽  
Airway Walls ◽  
Α2β1 Integrin ◽  
Airway Cells

Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of β1-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n = 47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α2 integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α1 and α2 integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α2 integrin chain. Expression of α2β1 integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α2β1 integrin on blood and airway CD8+ T-cells. Thicker airway walls in CT were associated with lower α2 integrin chain on blood CD4+ T-cells and airway eosinophils. Our data suggest that α2β1 integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.

scholarly journals Role of matrix metalloprotease-9 in hyperoxic injury in developing lung

2008 ◽  
Vol 295 (4) ◽  
pp. L584-L592 ◽  
Author(s):  
Anne Chetty ◽  
Gong-Jie Cao ◽  
Mariano Severgnini ◽  
Amy Simon ◽  
Rod Warburton ◽  
...  
Keyword(s):  
Lung Injury ◽  
Structural Changes ◽  
Type I Collagen ◽  
Alveolar Epithelium ◽  
Mouse Lung ◽  
Type I ◽  
Matrix Metalloprotease ◽  
Oxidant Injury ◽  
Hyperoxia Exposure

Matrix metalloprotease-9 (MMP-9) is increased in lung injury following hyperoxia exposure in neonatal mice, in association with impaired alveolar development. We studied the role of MMP-9 in the mechanism of hyperoxia-induced functional and histological changes in neonatal mouse lung. Reduced alveolarization with remodeling of ECM is a major morbidity component of oxidant injury in developing lung. MMP-9 mediates oxidant injury in developing lung causing altered lung remodeling. Five-day-old neonatal wild-type (WT) and MMP-9 (−/−) mice were exposed to hyperoxia for 8 days. The lungs were inflation fixed, and sections were examined for morphometry. The mean linear intercept and alveolar counts were evaluated. Immunohistochemistry for MMP-9 and elastin was performed. MMP-2, MMP-9, type I collagen, and tropoelastin were measured by Western blot analysis. Lung quasistatic compliance was studied in anaesthetized mice. MMP-2 and MMP-9 were significantly increased in lungs of WT mice exposed to hyperoxia compared with controls. Immunohistochemistry showed an increase in MMP-9 in mesenchyme and alveolar epithelium of hyperoxic lungs. The lungs of hyperoxia-exposed WT mice had less gas exchange surface area and were less compliant compared with room air-exposed WT and hyperoxia-exposed MMP-9 (−/−) mice. Type I collagen and tropoelastin were increased in hyperoxia-exposed WT with aberrant elastin staining. These changes were ameliorated in hyperoxia-exposed MMP-9 (−/−) mice. MMP-9 plays an important role in the structural changes consequent to oxygen-induced lung injury. Blocking MMP-9 activity may lead to novel therapeutic approaches in preventing bronchopulmonary dysplasia.

scholarly journals Hydroxyl radical induced structural changes of collagen

2007 ◽  
Vol 21 (2) ◽  
pp. 91-103 ◽  
Author(s):  
Helan Xiao ◽  
Guoping Cai ◽  
Mingyao Liu
Keyword(s):  
Free Radical ◽  
Hydroxyl Radicals ◽  
Structural Changes ◽  
Type I Collagen ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Type I ◽  
Dependent Manner ◽  
First Time

Extracellular matrix (ECM) plays an important role in cell differentiation, growth, migration and apoptosis. Collagen is the most abundant protein familyin vivo, but its function has still not been clearly defined yet. Reactive oxygen species (ROS) have a central role in oxidative cell stress. Electron spin resonance (ESR) spectroscopy indicates that type I collagen could uniquely scavenge hydroxyl radicals in dose- and time-dependent manner; whereas BSA and gelatin (a denatured collagen) have no such an effect. However, the mechanism by which type I collagen scavenges hydroxyl radicals is different from that of GSH, a well-known free radical scavenger. Using a new method, two-dimensional FTIR correlation analysis, for the first time, we show that the order of functional group changes of type I collagen in this process is amide I earlier than amide II than amide III than –CH– thanν(C=O). The results indicates that the structure of the main chain of collagen changed first, followed by more residue groupν(C=O) exposed to hydroxyl radicals. The reaction with the carbonyl group in collagen causes the hydroxyl free radicals to be scavenged. Therefore, ECM can effectively scavenge ROS under normal physiological conditions. When the proteins of ECM were denatured in the same way as gelatin, they lost their function as a free radical scavenger. All of these results provide new insight into therapy or prevention of oxidative stress, apoptosis and ageing.

Metastatic Dissemination of Human Ovarian Epithelial Carcinoma Is Promoted by α2β1-Integrin-Mediated Interaction with Type I Collagen

1998 ◽  
Vol 18 (1) ◽  
pp. 15-26 ◽  
Author(s):  
David A. Fishman ◽  
Alicia Kearns ◽  
Krishna Chilukuri ◽  
Lisa M. Bafetti ◽  
Edel A. O’Toole ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Type I ◽  
Metastatic Dissemination ◽  
Ovarian Epithelial Carcinoma ◽  
Α2β1 Integrin

Platelet α2β1 integrin activation: contribution of ligand internalization and the α2-cytoplasmic domain

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1307-1315 ◽  
Author(s):  
Zhengyan Wang ◽  
Tina M. Leisner ◽  
Leslie V. Parise
Keyword(s):  
Type I Collagen ◽  
Cytoplasmic Tail ◽  
Fluorescein Isothiocyanate ◽  
Activation Process ◽  
Type I ◽  
Collagen Binding ◽  
Cell Permeable Peptide ◽  
A Cell ◽  
Collagen Receptor ◽  
Α2β1 Integrin

Abstract The α2β1 integrin is a major collagen receptor on platelets. Although it has been proposed that α2β1, like αIIbβ3, undergoes agonist-induced activation, neither the potential contributions of α2β1 receptor/ligand internalization to the increase in ligand binding nor the roles of the α2 and β1 cytoplasmic domains in activation of this integrin have been previously explored. Activation of α2β1 was assessed with fluorescein isothiocyanate–labeled soluble type I collagen binding to platelets by flow cytometry. Although collagen internalization in response to agonist activation of platelets was significant, agonist-induced collagen binding still occurred under conditions that block internalization, with minimal changes in cell surface α2β1 expression. Introduction of cell-permeable peptides containing the α2 cytoplasmic tail, and especially the membrane proximal KLGFFKR domain, induced α2β1 activation in resting platelets, whereas a cell-permeable peptide containing the β1 cytoplasmic tail was without effect. Thus, collagen binding to stimulated platelets is increased due to α2β1 activation, in addition to internalization, and the GFFKR motif appears to play an important role in the activation process.

scholarly journals Crosstalk between the α2β1 integrin and c-met/HGF-R regulates innate immunity

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3562-3570 ◽  
Author(s):  
Karissa D. McCall-Culbreath ◽  
Zhengzhi Li ◽  
Mary M. Zutter
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Innate Immune Response ◽  
Cell Activation ◽  
Type I Collagen ◽  
Innate Immune ◽  
Mast Cell Activation ◽  
Type I ◽  
Matrix Metalloproteinase 1 ◽  
Α2β1 Integrin

AbstractData from several investigators suggest that the α2β1 integrin, a receptor for collagens, laminins, decorin, E-cadherin, matrix metalloproteinase-1, endorepellin, and several viruses, is required for innate immunity and regulation of autoimmune/allergic disorders. We demonstrated that the innate immune response to Listeria monocytogenes required α2β1 integrin expression by peritoneal mast cells (PMCs). Ligation of the α2β1 integrin by C1q contained in immune complexes comprised of Listeria and antibody was required for PMC activation in vitro and in vivo. However, ligation of the α2β1 integrin alone was insufficient to activate cytokine secretion, suggesting that one or more additional signals emanating from a coreceptor were required for PMC activation. Here, we demonstrate that C1q, but neither other complement proteins nor FcRγ, is required for early innate immune response to Listeria. The binding of Listeria's Internalin B (InlB) to hepatocyte growth factor receptor (HGF-R)/c-met provides the costimulatory function required for PMC activation. Either HGF or Listeria InlB bound to c-met and either C1q or type I collagen bound to α2β1 integrin stimulates PMC activation. These findings suggest that crosstalk between c-met and the α2β1 integrin may contribute to mast-cell activation in autoimmune and inflammatory disorders.

scholarly journals Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3489 ◽  
Author(s):  
Luciana S. Oliveira ◽  
Maria Inácia Estevão-Costa ◽  
Valéria G. Alvarenga ◽  
Dan E. Vivas-Ruiz ◽  
Armando Yarleque ◽  
...  
Keyword(s):  
Metal Ion ◽  
Type I Collagen ◽  
Divalent Cations ◽  
Type I ◽  
Glycoprotein Vi ◽  
Rich Domain ◽  
Multidomain Structure ◽  
A1 Domain ◽  
Bothrops Atrox ◽  
Α2β1 Integrin

Atroxlysin-III (Atr-III) was purified from the venom of Bothrops atrox. This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase. Its cDNA-deduced amino acid sequence reveals a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-like and a cysteine-rich domain. Its identity with bothropasin and jararhagin from Bothrops jararaca is 97% and 95%, respectively. Its enzymatic activity is metal ion-dependent. The divalent cations, Mg2+ and Ca2+, enhance its activity, whereas excess Zn2+ inhibits it. Chemical modification of the Zn2+-complexing histidine residues within the active site by using diethylpyrocarbonate (DEPC) inactivates it. Atr-III degrades plasma fibronectin, type I-collagen, and mainly the α-chains of fibrinogen and fibrin. The von Willebrand factor (vWF) A1-domain, which harbors the binding site for GPIb, is not hydrolyzed. Platelets interact with collagen via receptors for collagen, glycoprotein VI (GPVI), and α2β1 integrin. Neither the α2β1 integrin nor its collagen-binding A-domain is fragmented by Atr-III. In contrast, Atr-III cleaves glycoprotein VI (GPVI) into a soluble ~55-kDa fragment (sGPVI). Thereby, it inhibits aggregation of platelets which had been stimulated by convulxin, a GPVI agonist. Selectively, Atr-III targets GPVI antagonistically and thus contributes to the antithrombotic effect of envenomation by Bothrops atrox.

Abstract 17939: Lack of the Alpha-11 Integrin in the Heart is Associated With Progressive Diastolic Dysfunction, Myofibrillar Disarray and Impaired Cardiomyocyte Growth

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Robert A Civitarese ◽  
Ilana Talior-Volodarsky ◽  
Melissa Mitchell ◽  
Jean-François Desjardins ◽  
Golam Kabir ◽  
...  
Keyword(s):  
Diastolic Function ◽  
Connexin 43 ◽  
Structural Changes ◽  
Type I Collagen ◽  
Heart Weight ◽  
Type I ◽  
Cardiovascular Development ◽  
Loop Analysis ◽  
Structural Examination ◽  
And Function

BACKGROUND: Integrins, transmembrane receptors, play crucial roles in diverse cellular and developmental processes due to critical interactions with the extracellular matrix (ECM). During fetal development and towards adulthood, heart growth and function is suggested to depend on forming and remodeling the ECM and its connection to the myocyte. Currently however, the role of integrins in cardiovascular development (CVD) is poorly defined. Thus, we hypothesized that the α11 integrin (α11), which is expressed by fibroblasts and binds preferentially to type I collagen fibers, plays a vital role in CVD. METHODS: α11 KO and wildtype littermate mice (both n = 8) were examined at 4 weeks and 8 weeks of age. Animals underwent function assessments, including echocardiography and invasive pressure volume (PV) loop analysis, and structural examination via histological and electron microscopy (EM) analysis. RESULTS: At 4 weeks, heart weight (HW) and HW indexed to tibial length were decreased in α11 KO mice (P < 0.05), which were normalized at 8 weeks. Echocardiography revealed reduced end-diastolic area (EDA) at 4 weeks (P < 0.05). Despite normalization of EDA at 8 weeks, PV loop revealed impaired diastolic function as evidence by increased EDP, prolonged Tau and steeper EDPVR (all P < 0.05). No differences in HR or systolic parameters were evident. α11 KO mice also demonstrated structural changes. WGA staining revealed evidence of myofibrillar disarray. Connexin 43 and desmin staining showed increased Z-disk and intermediate filament clustering, respectively. LV myocyte size was also reduced (P < 0.05). Similarly, EM analysis showed reduced cardiomyocyte thickness and distance between end plates (both P < 0.05). CONCLUSION: Loss of α11 resulted in progressively worsening diastolic function that was associated with myofibrillar disarray and impaired cardiomyocyte growth. These findings suggest that α11 is required for the development of normal heart structure and function.

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