Identification of Glycosaminoglycans in Human Airway Secretions

Monzón, Maria E.; Casalino‐Matsuda, S. Marina; Forteza, Rosanna

doi:10.1165/rcmb.2005-0256oc

Cited by 65 publications

(63 citation statements)

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“…These results are in agreement with the reported presence of heparin, chondroitin and DS in tracheal tissue sections [9] and of HA in the human lung [11][12][13]. However, we observed that total GAG synthesis was reduced in ASMC from asthma and COPD patients when compared with controls.…”

Section: Discussionsupporting

confidence: 93%

“…The function of these GAG varies within the organ in which they are located. In the human lung, KS was found on the apical surface of ciliated epithelial cells, CS and DS were secreted by epithelial and submucosa gland cells, and HS was reported in the ECM of tracheal tissue sections [9]. HA and the enzymes that metabolise it are also endogenous to the pulmonary environment, and HA has been isolated from the lungs of mammals (sheep, guinea pig and rat) [10], and human lung parenchyma and pleura [11].…”

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confidence: 99%

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Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD

Klagas¹,

Goulet²,

Karakiulakis³

et al. 2009

European Respiratory Journal

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Glycosaminoglycans (GAG) are essential extracellular matrix molecules which regulate tissue flexibility, a parameter that is reduced in airways of patients with asthma and chronic obstructive pulmonary disease (COPD). We investigated the expression of GAG and their metabolising enzymes in primary human airway smooth muscle cells (ASMC) obtained from healthy donors (controls) and patients with asthma or COPD.Total GAG synthesis was assessed by [ 3 H]-glucosamine incorporation. GAG were isolated, purified, fractionated by electrophoresis and characterised using specific GAG-degrading enzymes. Secretion of hyaluronic acid (HA) by ASMC from patients with asthma or COPD was significantly decreased compared with controls. RT-PCR analysis and western blotting revealed that this decrease was associated with a significant reduction in the expression of HA synthase-1 and -2 and a significant increase of hyaluronidase-1. Furthermore, the expression of the HA receptor CD44 was significantly decreased, whereas the receptor for HA-mediated motility was not expressed in asthma or COPD.Our results indicate that there is a decreased expression of HA in asthma and COPD associated with a synergistic regulation of HA metabolising enzymes that may regulate the pathological airway remodelling in these lung diseases.

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD

Klagas¹,

Goulet²,

Karakiulakis³

et al. 2009

European Respiratory Journal

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“…Supernatants were precipitated with ethanol, freeze-dried and prepared for the assessment of HA amounts by fluorophore-assisted carbohydrate electrophoresis (FACE) analysis as previously described (16,42) or HA size as described below.…”

Section: Ha Contentmentioning

confidence: 99%

“…It is released by submucosal glands and by superficial airway epithelial cells (16,17) where it serves as an anchor for secreted proteins involved in host defense, preventing their removal by mucociliary clearance (18 -20). Tissue kallikrein (TK), a serine protease involved in airway inflammation and mucus hypersecretion (15,21) is bound to, and inhibited by HMWHA at the airway epithelial surface.…”

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confidence: 99%

Reactive Oxygen Species and Hyaluronidase 2 Regulate Airway Epithelial Hyaluronan Fragmentation

Monzón

Fregien

Schmid

et al. 2010

Journal of Biological Chemistry

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100

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Hyaluronidase 2 (Hyal2) is a hyaluronan (HA)-degrading enzyme found intracellularly or/and anchored to the plasma membrane through glycosylphosphatidylinositol (GPI). Normal human bronchial epithelial cells (NHBE) grown at the air-liquid interphase (ALI), treated with PI-specific phospholipase C (PI-PLC), exhibited increased Hyal activity in secretions and decreased protein and activity on the apical membrane, confirming that GPI-anchored Hyal2 is expressed in NHBE cells and it remains active in its soluble form. We have reported that HA degradation was mediated by reactive oxygen species (ROS) in human airways. Here we show that ROS increase Hyal2 expression and activity in NHBE cells and that the p38MAPK signaling pathway is involved in this effect. Hyal2 induction was confirmed by using small interfering RNA (siRNA) expressing lentivirus. These in vitro findings correlated in vivo with smokers, where increased Hyal2 immunoreactivity in the epithelium was associated with augmented levels of HA and the appearance of low molecular mass HA species in bronchial secretions. In summary, this work provides evidence that ROS induce Hyal2, suggesting that Hyal2 is likely responsible for the sustained HA fragmentation in the airway lumen observed in inflammatory conditions associated with oxidative stress. Hyaluronan (HA)3 is a non-sulfated glycosaminoglycan found in the extracellular matrix, in body fluids, and in secretions of mammals. HA is synthesized by three transmembrane isoenzymes: HAS1, HAS2, and HAS3 at the inner face of the plasma membrane and translocated into the extracellular space (1).The association with various binding proteins (2, 3) confers HA with a unique plasticity to organize extracellular matrix (ECM) in a tissue specific fashion (for review see Ref. 4), varying from a tightly cross-linked mesh in cartilage to a highly hydrated matrix in dermis and vitreous humor (5).In addition, HA induces intracellular signaling by binding specific receptors at the cell surface, (6, 7) orchestrating a variety of host responses generally requiring an extensive deposition of a HA in the ECM. This deposition is essential for cumulus oophorus fertilization (8) as well as for proliferation and migration of mesenchymal cells. Airway smooth muscle cells exposed to polyinosinic acid-polycytidylic acid synthesize an abnormal HA matrix with cable-like structures that bind and retains leukocytes (9, 10), suggesting that HA play key roles on host defense against infections as well.Biological functions of HA are associated with its size (6, 11). For instance, high molecular weight HA (HMWHA) exhibit anti-angiogenic, anti-inflammatory, and immunosuppressive effects while small HA fragments are angiogenic and proinflammatory (12, 13). The contrasting responses elicited by different sizes of HA are exemplified in a recent report in which HMWHA attenuated while low molecular weight HA (LMWHA) increased ozone-induced airway hyperreactivity, in a mouse model of asthma (14).In human airway epithelium, HA is present at the lumen as...

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“…Endogenous HMW HA plays a pivotal role in the homeostasis of the upper and the lower airways: it is an important component of the normal airway secretions, exerts anti-inflammatory and antiangiogenic actions, promotes cell survival and mucociliary clearance, organizes extracellular matrix, stabilizes connective tissues, sustains healing processes and regulates tissues hydration [144,[232][233][234]. Hence, exogenous HMW HA represents a promising therapeutic agent for the treatment of nasal and lung diseases that involve inflammation, oxidative stress and epithelial remodeling, such as allergic and non-allergic rhinitis, asthma, chronic obstructive pulmonary disease and cystic fibrosis [143,233,[235][236][237][238].…”

Section: Rhinology and Pneumologymentioning

confidence: 99%

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Fallacara¹,

Baldini²,

Manfredini³

et al. 2018

Preprint

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Since its first isolation in 1934, hyaluronic acid (HA) has been studied across a variety of research areas. This unbranched glycosaminoglycan consisting of repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid is almost ubiquitary in humans and in other vertebrates. HA is involved in many key processes -including cell signaling, wound reparation, tissue regeneration, morphogenesis, matrix organization and pathobiology-, and has unique physico-chemical properties -such as biocompatibility, biodegradability, mucoadhesivity, hygroscopicity and viscoelasticity. For these reasons, exogenous HA has been investigated as drug delivery system and treatment in cancer, ophthalmology, arthrology, pneumology, rhinology, urology, aesthetic medicine and cosmetic. To improve and customize its properties and applications, HA can be subjected to chemical modifications: conjugation and crosslinking. The present review gives an overview regarding HA, describing its history, physico-chemical, structural and hydrodynamic properties, and biology -occurrence, biosynthesis (by hyaluronan synthases), degradation (by hyaluronidases and oxidative stress), roles, mechanisms of action and receptors. Furthermore, both conventional and recently emerging methods developed for the industrial production of HA and its chemical derivatization are presented. Finally, the medical, pharmaceutical and cosmetic applications of HA and its derivatives are reviewed, reporting examples of HA-based products which currently are on the market or are undergoing further investigations.

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Identification of Glycosaminoglycans in Human Airway Secretions

Cited by 65 publications

References 48 publications

Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD

Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD

Reactive Oxygen Species and Hyaluronidase 2 Regulate Airway Epithelial Hyaluronan Fragmentation

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

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