Modified High-Molecular-Weight Hyaluronan Promotes Allergen-Specific Immune Tolerance.

Abstract:

:The extracellular matrix in asthmatic lungs contains abundant low-molecular-weight hyaluronan, and this is known to promote antigen presentation and allergic responses. Conversely, high-molecular-weight hyaluronan (HMW-HA), typical of uninflamed tissues, is known to suppress inflammation. We investigated whether HMW-HA can be adapted to promote tolerance to airway allergens. HMW-HA was thiolated to prevent its catabolism and was tethered to allergens via thiol linkages. This platform, which we call "XHA," delivers antigenic payloads in the context of antiinflammatory costimulation. Allergen/XHA was administered intranasally to mice that had been sensitized previously to these allergens. XHA prevents allergic airway inflammation in mice sensitized previously to either ovalbumin or cockroach proteins. Allergen/XHA treatment reduced inflammatory cell counts, airway hyperresponsiveness, allergen-specific IgE, and T helper type 2 cell cytokine production in comparison with allergen alone. These effects were allergen specific and IL-10 dependent. They were durable for weeks after the last challenge, providing a substantial advantage over the current desensitization protocols. Mechanistically, XHA promoted CD44-dependent inhibition of nuclear factor-κB signaling, diminished dendritic cell maturation, and reduced the induction of allergen-specific CD4 T-helper responses. XHA and other potential strategies that target CD44 are promising alternatives for the treatment of asthma and allergic sinusitis.

authors

Gebe JA,Yadava K,Ruppert SM,Marshall P,Hill P,Falk BA,Sweere JM,Han H,Kaber G,Harten IA,Medina C,Mikecz K,Ziegler SF,Balaji S,Keswani SG,Perez VA,Butte MJ,Nadeau K,Altemeier WA,Fanger N,Bollyky PL

doi

10.1165/rcmb.2016-0111OC

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

109-120

issue

1

eissn

1044-1549

issn

1535-4989

journal_volume

56

pub_type

杂志文章
  • Respirable coal dust particles modify cytochrome P4501A1 (CYP1A1) expression in rat alveolar cells.

    abstract::Cytochrome P4501A1 (CYP1A1) metabolizes polycyclic aromatic hydrocarbons in cigarette smoke to DNA-binding reactive intermediates associated with carcinogenesis. Epidemiologic studies indicate that the majority of coal miners are smokers but have a lower risk of lung cancer than other smokers. We hypothesized that coa...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2003-0425OC

    authors: Ghanem MM,Porter D,Battelli LA,Vallyathan V,Kashon ML,Ma JY,Barger MW,Nath J,Castranova V,Hubbs AF

    更新日期:2004-08-01 00:00:00

  • Ozone enhances pulmonary innate immune response to a Toll-like receptor-2 agonist.

    abstract::Previous work demonstrated that pre-exposure to ozone primes innate immunity and increases Toll-like receptor-4 (TLR4)-mediated responses to subsequent stimulation with LPS. To explore the pulmonary innate immune response to ozone exposure further, we investigated the effects of ozone in combination with Pam3CYS, a sy...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2012-0187OC

    authors: Oakes JL,O'Connor BP,Warg LA,Burton R,Hock A,Loader J,Laflamme D,Jing J,Hui L,Schwartz DA,Yang IV

    更新日期:2013-01-01 00:00:00

  • Cyclic AMP-mobilizing agents and glucocorticoids modulate human smooth muscle cell migration.

    abstract::Hyperplasia and cell migration of smooth muscle are features of both airway and pulmonary vascular diseases. The precise cellular and molecular mechanisms that regulate smooth muscle migration in the lungs remain unknown. In this study, we examined the effect of cAMP-mobilizing agents and steroids on smooth muscle cel...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2002-0254OC

    authors: Goncharova EA,Billington CK,Irani C,Vorotnikov AV,Tkachuk VA,Penn RB,Krymskaya VP,Panettieri RA Jr

    更新日期:2003-07-01 00:00:00

  • Pluripotent allospecific CD8+ effector T cells traffic to lung in murine obliterative airway disease.

    abstract::Long-term success in lung transplantation is limited by obliterative bronchiolitis, whereas T cell effector mechanisms in this process remain incompletely understood. Using the mouse heterotopic allogeneic airway transplant model, we studied T cell effector responses during obliterative airways disease (OAD). Allospec...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2005-0164OC

    authors: West EE,Lavoie TL,Orens JB,Chen ES,Ye SQ,Finkelman FD,Garcia JG,McDyer JF

    更新日期:2006-01-01 00:00:00

  • DNA double-strand breaks by asbestos, silica, and titanium dioxide: possible biomarker of carcinogenic potential?

    abstract::DNA double-strand breaks (DSBs) can result in cell death or genetic alterations when cells are subjected to radiation, exposure to toxins, or other environmental stresses. A complex DNA-damage-response pathway is activated to repair the damage, and the inability to repair these breaks can lead to carcinogenesis. One o...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2009-0062OC

    authors: Msiska Z,Pacurari M,Mishra A,Leonard SS,Castranova V,Vallyathan V

    更新日期:2010-08-01 00:00:00

  • Immobilized IgG immune complex induces secretion of tumor necrosis factor-alpha by porcine alveolar macrophages.

    abstract::Tumor necrosis factor-alpha (TNF-alpha) is an important inflammatory mediator produced by activated monocytes and macrophages. We have previously shown that porcine alveolar macrophages (PAM) mediate bystander cytotoxicity through hydrogen peroxide production following activation with immobilized IgG immune complex (I...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/5.3.249

    authors: Kim JW,Wierda WG,Kim YB

    更新日期:1991-09-01 00:00:00

  • Early-passage rat lung fibroblasts do not migrate in vitro to transforming growth factor-beta.

    abstract::Lung fibrosis has been postulated to be mediated by the production of macrophage-derived growth factors that are both mitogenic and chemotactic for fibroblasts. In vitro studies from our laboratory demonstrated that alveolar and interstitial macrophages treated with iron and asbestos release platelet-derived growth fa...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/8.5.468

    authors: Osornio-Vargas AR,Kalter VG,Badgett A,Hernández-Rodríguez N,Aguilar-Delfín I,Brody AR

    更新日期:1993-05-01 00:00:00

  • Genetic ablation of the fpr1 gene confers protection from smoking-induced lung emphysema in mice.

    abstract::Cigarette smoke (CS) is the main causative factor of chronic obstructive pulmonary disease (COPD). Current research supports the concept that airway inflammation is central to the development and progression of the disease. Studies have demonstrated that neutrophils are increased in COPD lungs and that neutrophil-asso...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2012-0036OC

    authors: Cardini S,Dalli J,Fineschi S,Perretti M,Lungarella G,Lucattelli M

    更新日期:2012-09-01 00:00:00

  • Deficiency in Nrf2-GSH signaling impairs type II cell growth and enhances sensitivity to oxidants.

    abstract::Redox imbalance has been implicated in the pathogenesis of many acute and chronic lung diseases. The b-Zip transcription factor Nrf2 acts via an antioxidant/electrophilic response element to regulate antioxidants and maintain cellular redox homeostasis. Our previous studies have shown that Nrf2-deficient mice (Nrf2(-/...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0004RC

    authors: Reddy NM,Kleeberger SR,Cho HY,Yamamoto M,Kensler TW,Biswal S,Reddy SP

    更新日期:2007-07-01 00:00:00

  • Neutrophil-Expressed p21/waf1 Favors Inflammation Resolution in Pseudomonas aeruginosa Infection.

    abstract::Neutrophil-associated inflammation during Pseudomonas aeruginosa lung infection is a determinant of morbidity in cystic fibrosis (CF). Neutrophil apoptosis is a key factor in inflammation resolution and is controlled by cytosolic proliferating cell nuclear antigen (PCNA). p21/Waf1, a cyclin-dependent kinase inhibitor,...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2015-0047OC

    authors: Martin C,Ohayon D,Alkan M,Mocek J,Pederzoli-Ribeil M,Candalh C,Thevenot G,Millet A,Tamassia N,Cassatella MA,Thieblemont N,Burgel PR,Witko-Sarsat V

    更新日期:2016-05-01 00:00:00

  • Effect of the plant derivative Compound A on the production of corticosteroid-resistant chemokines in airway smooth muscle cells.

    abstract::Preclinical models of human conditions including asthma showed the therapeutic potential of Compound A (CpdA), a dissociated glucocorticoid (GC) receptor (GRα) ligand. Whether CpdA inhibits GC resistance, a central feature of severe asthma, has not been addressed. We investigated whether CpdA modulates cytokine-induce...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2014-0477OC

    authors: Gavrila A,Chachi L,Tliba O,Brightling C,Amrani Y

    更新日期:2015-11-01 00:00:00

  • Persistence of serotonergic enhancement of airway response in a model of childhood asthma.

    abstract::The persistence of airway hyperresponsiveness (AHR) and serotonergic enhancement of airway smooth muscle (ASM) contraction induced by ozone (O3) plus allergen has not been evaluated. If this mechanism persists after a prolonged recovery, it would indicate that early-life exposure to O3 plus allergen induces functional...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0387OC

    authors: Moore BD,Hyde DM,Miller LA,Wong EM,Schelegle ES

    更新日期:2014-07-01 00:00:00

  • Transcriptional activation of the HO-1 gene by lipopolysaccharide is mediated by 5' distal enhancers: role of reactive oxygen intermediates and AP-1.

    abstract::Heme oxygenase-1 (HO-1) is a stress-response protein, the expression of which is transcriptionally regulated by agents that cause oxidative stress. We have previously shown that lipopolysaccharide (LPS)-induced HO-1 gene transcription in RAW 264.7 macrophage cells is mediated by a distal enhancer called SX2, located 4...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.18.2.2910

    authors: Camhi SL,Alam J,Wiegand GW,Chin BY,Choi AM

    更新日期:1998-02-01 00:00:00

  • Z and S mutations of the alpha1-antitrypsin gene and the risk of chronic obstructive pulmonary disease.

    abstract::Chronic obstructive pulmonary disease (COPD) has been associated with heterozygosity for the Z and S alleles of the alpha1-antitrypsin gene in some studies, but these observations have not been confirmed by others. Cigarette smoking is the major risk factor for COPD and may have been a confounding factor in many of th...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.20.2.3177

    authors: Sandford AJ,Weir TD,Spinelli JJ,Paré PD

    更新日期:1999-02-01 00:00:00

  • Long-Term Microevolution of Pseudomonas aeruginosa Differs between Mildly and Severely Affected Cystic Fibrosis Lungs.

    abstract::Chronic airway infections with Pseudomonas aeruginosa determine morbidity in most individuals with cystic fibrosis (CF). P. aeruginosa may persist for decades in CF lungs, which provides a rare opportunity to study the long-term within-host evolution of a bacterial airway pathogen. In this work, we sought to resolve t...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2017-0356OC

    authors: Klockgether J,Cramer N,Fischer S,Wiehlmann L,Tümmler B

    更新日期:2018-08-01 00:00:00

  • p42/44 Mitogen-activated protein kinase regulated by p53 and nitric oxide in human pulmonary arterial smooth muscle cells.

    abstract::Although nitric oxide (NO) is known to inhibit vascular smooth muscle cell proliferation, the subcellular molecular mechanisms involved with the inhibitory signal transduction pathways are uncertain. We investigated the effect of exogenous NO on cell proliferation and the expression of p53, p21, and phosphorylated p42...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2003-0397OC

    authors: Mizuno S,Kadowaki M,Demura Y,Ameshima S,Miyamori I,Ishizaki T

    更新日期:2004-08-01 00:00:00

  • German cockroach proteases regulate interleukin-8 expression via nuclear factor for interleukin-6 in human bronchial epithelial cells.

    abstract::German cockroach extract synergistically regulates tumor necrosis factor-alpha (TNF-alpha)-induced interleukin (IL)-8 expression in human airway epithelial cells. The IL-8 promoter contains nuclear factor (NF)-kappaB, activating protein (AP)-1, and NF for IL-6 (NF-IL6) transcription factor binding regions. Because coc...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2004-0231OC

    authors: Page K,Hughes VS,Odoms KK,Dunsmore KE,Hershenson MB

    更新日期:2005-03-01 00:00:00

  • High glucose enhances responsiveness of human airways smooth muscle via the Rho/ROCK pathway.

    abstract::Glucose moves into airway secretions after a glucose load. Therefore people with diabetes or hyperglycemia spend a significant proportion of each day with glucose in their airways secretions. This study investigated the effects of glucose on isolated human airways and on cultured airway smooth muscle (ASM) cells. Huma...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2011-0449OC

    authors: Cazzola M,Calzetta L,Rogliani P,Lauro D,Novelli L,Page CP,Kanabar V,Matera MG

    更新日期:2012-10-01 00:00:00

  • Inhaled asbestos fibers induce p53 expression in the rat lung.

    abstract::Humans and rodents exposed to an aerosol of asbestos fibers develop lung injury that can lead to a fibroproliferative response culminating in excessive scarring and impaired lung function. To define the early events that precede asbestos-induced fibrotic lung disease, rats were exposed to an aerosol of chrysotile asbe...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.16.4.9115760

    authors: Mishra A,Liu JY,Brody AR,Morris GF

    更新日期:1997-04-01 00:00:00

  • β2-Adrenoceptor agonists are required for development of the asthma phenotype in a murine model.

    abstract::β(2)-Adrenoceptor (β2AR) agonists are the most effective class of bronchodilators and a mainstay of asthma management. The first potent β2AR agonist discovered and widely used in reversing the airway constriction associated with asthma exacerbation was the endogenous activator of the β2AR, epinephrine. In this study, ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2012-0364OC

    authors: Thanawala VJ,Forkuo GS,Al-Sawalha N,Azzegagh Z,Nguyen LP,Eriksen JL,Tuvim MJ,Lowder TW,Dickey BF,Knoll BJ,Walker JK,Bond RA

    更新日期:2013-02-01 00:00:00

  • Quantitative trait analysis of nickel-induced acute lung injury in mice.

    abstract::The genetic determinants underlying susceptibility to acute lung injury have not been identified. Recently, we found that the strain distribution pattern for mean survival time (MST) to three irritants-ozone, ultrafine Teflon, and nickel sulfate- was shared between inbred mouse strains. For ozone-induced acute lung in...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.24.6.4303

    authors: Prows DR,Leikauf GD

    更新日期:2001-06-01 00:00:00

  • Dissection of the hyperadhesive phenotype of airway eosinophils in asthma.

    abstract::Asthma is characterized by appearance of eosinophils in the airway. Eosinophils purified from the airway 48 h after segmental antigen challenge are described as exhibiting greater adhesion to albumin-coated surfaces via an unidentified beta2 integrin and increased expression of alphaMbeta2 (CD11b/18) compared with pur...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2006-0027OC

    authors: Barthel SR,Jarjour NN,Mosher DF,Johansson MW

    更新日期:2006-09-01 00:00:00

  • Inhibition of ozone-induced nitric oxide synthase expression in the lung by endotoxin.

    abstract::Inhalation of the pulmonary irritant ozone is associated with an accumulation of macrophages in the lung. These cells, along with type II epithelial cells, are activated to release increased quantities of hydrogen peroxide and nitric oxide, two reactive mediators that have been implicated in tissue injury. In the pres...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.14.6.8652180

    authors: Pendino KJ,Gardner CR,Shuler RL,Laskin JD,Durham SK,Barton DS,Ohnishi ST,Ohnishi T,Laskin DL

    更新日期:1996-06-01 00:00:00

  • Neutrophil-endothelial interactions mediate angiopoietin-2-associated pulmonary endothelial cell dysfunction in indirect acute lung injury in mice.

    abstract::Unresolved inflammation in the lung is thought to elicit loss of endothelial cell (EC) barrier integrity and impaired lung function. We have shown, in a mouse model of shock/sepsis, that neutrophil interactions with resident pulmonary cells appear central to the pathogenesis of indirect acute lung injury (iALI). Norma...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0148OC

    authors: Lomas-Neira J,Venet F,Chung CS,Thakkar R,Heffernan D,Ayala A

    更新日期:2014-01-01 00:00:00

  • Targeting the MEK1 cascade in lung epithelium inhibits proliferation and fibrogenesis by asbestos.

    abstract::The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are phosphorylated after inhalation of asbestos. The effect of blocking this signaling pathway in lung epithelium is unclear. Asbestos-exposed transgenic mice expressing a dominant-negative mitogen-activated protein kinase kinase-1 (dnMEK1) (i.e., the upstrea...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0382OC

    authors: Manning CB,Sabo-Attwood T,Robledo RF,Macpherson MB,Rincón M,Vacek P,Hemenway D,Taatjes DJ,Lee PJ,Mossman BT

    更新日期:2008-05-01 00:00:00

  • Effects of epithelial cell supernatant on membrane potential and contraction of dog airway smooth muscles.

    abstract::We investigated the effects of cultured epithelial cells and supernatants on resting membrane potential and excitatory neuroeffector transmission in smooth muscle cells of dog trachea and bronchioles. The mean resting membrane potential of the mucosa-free tracheal smooth muscle cells was -59.5 +/- 1.5 mV (+/- SD). App...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.10.3.8117450

    authors: Matsumoto K,Aizawa H,Inoue R,Hamano S,Ikeda S,Xie Z,Hirata M,Hara N,Ito Y

    更新日期:1994-03-01 00:00:00

  • Epithelial sodium channel inhibition in primary human bronchial epithelia by transfected siRNA.

    abstract::Na(+) absorption and Cl(-) secretion are in equilibrium to maintain an appropriate airway surface fluid volume and ensure appropriate mucociliary clearance. In cystic fibrosis, this equilibrium is disrupted by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in the absence of ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0456OC

    authors: Caci E,Melani R,Pedemonte N,Yueksekdag G,Ravazzolo R,Rosenecker J,Galietta LJ,Zegarra-Moran O

    更新日期:2009-02-01 00:00:00

  • Tuberculosis susceptibility of diabetic mice.

    abstract::Increased susceptibility to infections, including tuberculosis (TB), is a major cause of morbidity and mortality in patients with diabetes. Despite the clinical importance of this problem, little is known about how diabetes impairs protective immunity. We modeled this phenomenon by infecting acute (< or = 1 mo) or chr...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2006-0478OC

    authors: Martens GW,Arikan MC,Lee J,Ren F,Greiner D,Kornfeld H

    更新日期:2007-11-01 00:00:00

  • Idiopathic pneumonia syndrome after allogeneic bone marrow transplantation in mice. Role of pretransplant radiation conditioning.

    abstract::Idiopathic pneumonia syndrome (IPS) is a significant clinical problem encountered among patients treated with bone marrow transplantation (BMT). IPS is identified as an inflammatory lung disease characterized by diffuse interstitial pneumonitis and alveolitis leading to interstitial fibrosis in the absence of an ident...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.20.6.3455

    authors: Shankar G,Scott Bryson J,Darrell Jennings C,Kaplan AM,Cohen DA

    更新日期:1999-06-01 00:00:00

  • CC chemokine receptor 3 mobilizes to the surface of human mast cells and potentiates immunoglobulin E-dependent generation of interleukin 13.

    abstract::Eotaxins-1, -2, and -3 mediate the recruitment of blood-borne eosinophils to allergically inflamed tissues by binding CC chemokine receptor (CCR) 3. Mast cells (MCs) are resident tissue cells that also express CCR3. In the present study, we demonstrate that human (h) MCs in nasal polyps and cultured cord blood-derived...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2002-0155OC

    authors: Price KS,Friend DS,Mellor EA,De Jesus N,Watts GF,Boyce JA

    更新日期:2003-04-01 00:00:00