Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation

Gerdin, Bengt; Hällgren, Roger

doi:10.1046/j.1365-2796.1997.00173.x

Cited by 123 publications

(103 citation statements)

References 41 publications

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“…Inflammation, infection, or physical damage can lead to the release of soluble GAGs. An inflammatory reaction, irrespective of its cause, is followed by increased synthesis of HA in the interstitium (30). GAGs are secreted during the activation of various cells, for example, endothelial and T cells (30,31).…”

Section: Discussionmentioning

confidence: 99%

“…An inflammatory reaction, irrespective of its cause, is followed by increased synthesis of HA in the interstitium (30). GAGs are secreted during the activation of various cells, for example, endothelial and T cells (30,31). Furthermore, bacterial pathogens display GAGs or GAG-like polysaccharide antigens on their surfaces, for example, group A streptococci possess an HA-rich capsule (32).…”

Section: Discussionmentioning

confidence: 99%

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Glycosaminoglycans are a potential cause of rheumatoid arthritis

Wang

Roehrl²

2002

Proc. Natl. Acad. Sci. U.S.A.

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Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory disease of connective tissue with unknown etiology. We investigated whether aberrant immune responses to glycosaminoglycans (GAGs), a major component of joint cartilage, joint fluid, and other soft connective tissue, causes this disease. Here we show that injection of GAGs such as hyaluronic acid, heparin, and chondroitin sulfates A, B, and C induce arthritis, tendosynovitis, dermatitis, and other pathological conditions in mice. We developed a technique by staining tissue specimens with fluorochrome-or biotin-labeled GAGs to visualize the direct binding between cells and GAGs. We discovered that inflammatory infiltrates from the affected tissue are dominated by a distinct phenotype of GAG-binding cells, a significant portion of which are CD4 ؉ T cells. GAG-binding cells seem to be expanded in bone marrow of GAG-immunized mice. Furthermore, we identified GAG-binding cells in inflamed synovial tissue of human patients with RA. Our findings suggest that carbohydrate self-antigenic GAGs provoke autoimmune dysfunctions that involve the expansion of GAG-binding cells which migrate to anatomical sites rich in GAGs. These GAG-binding cells might, in turn, promote the inflammation and pathology seen both in our murine model and in human RA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Glycosaminoglycans are a potential cause of rheumatoid arthritis

Wang

Roehrl²

2002

Proc. Natl. Acad. Sci. U.S.A.

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“…Hyaluronan accumulates in the extracellular matrix and in serum in many inflammatory states, and often the serum level correlates with the degree of inflammation (6,7). Several studies have demonstrated that activated leukocytes can bind to endothelial cell HA (8 -12), and we recently demonstrated that leukocytes can bind to virally infected SMCs via novel structures formed by HA (13,14).…”

mentioning

confidence: 99%

Endoplasmic Reticulum Stress Induces Hyaluronan Deposition and Leukocyte Adhesion

Majors

Austin

Motte³

et al. 2003

Journal of Biological Chemistry

137

140

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There is mounting evidence that perturbations in endoplasmic reticulum (ER) function play a key role in the pathogenesis of a broad range of diseases. We have examined the ability of ER stress to modulate leukocyte binding to colonic and aortic smooth muscle cells. In vitro, control smooth muscle cells bind few leukocytes, but treatment with compounds that induce ER stress, including tunicamycin, A23187, and thapsigargin, promotes leukocyte binding. Likewise, dextran sulfate, another agent capable of inducing ER stress and promoting inflammation in vivo, strongly induces leukocyte adhesion. The bound leukocytes are released by hyaluronidase treatment, indicating a critical role for hyaluronan-containing structures in mediating leukocyte binding. Affinity histochemistry demonstrated that hyaluronan accumulates and is present in cable-like structures in the treated, but not the untreated, cultures and that these structures serve as attachment sites for leukocytes. Hyaluronan-rich regions of both murine and human inflamed colon contain numerous cells that stain intensely for ER-resident chaperones containing the KDEL sequence, demonstrating a relationship between ER stress and hyaluronan deposition in vivo. These results indicate that ER stress may contribute to chronic inflammation by forming a hyaluronan-rich extracellular matrix that is conducive to leukocyte binding.

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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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Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation

Cited by 123 publications

References 41 publications

Glycosaminoglycans are a potential cause of rheumatoid arthritis

Glycosaminoglycans are a potential cause of rheumatoid arthritis

Endoplasmic Reticulum Stress Induces Hyaluronan Deposition and Leukocyte Adhesion

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

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