title: Hyaluronan fragments as mediators of inflammation in allergic pulmonary disease.
abstract: Asthma is frequently caused and/or exacerbated by sensitization to allergens, which are ubiquitous in many indoor and outdoor environments. Severe asthma is characterized by airway hyperresponsiveness and bronchial constriction in response to an inhaled allergen, leading to a disease course that is often very difficult to treat with standard asthma therapies. As a result of interactions among inflammatory cells, structural cells, and the intercellular matrix of the allergic lung, patients with sensitization to allergens may experience a greater degree of tissue injury followed by airway wall remodeling and progressive, accumulated pulmonary dysfunction as part of the disease sequela. In addition, turnover of extracellular matrix (ECM) components is a hallmark of tissue injury and repair. This review focuses on the role of the glycosaminoglycan hyaluronan (HA), a component of the ECM, in pulmonary injury and repair with an emphasis on allergic asthma. Both the synthesis and degradation of the ECM are critical contributors to tissue repair and remodeling. Fragmented HA accumulates during tissue injury and functions in ways distinct from the larger native polymer. There is gathering evidence that HA degradation products are active participants in stimulating the expression of inflammatory genes in a variety of immune cells at the injury site. In this review, we will consider recent advances in the understanding of the mechanisms that are associated with HA accumulation and inflammatory cell recruitment in the asthmatic lung.
authors.affiliation: Department of Veterinary and Microbiological Sciences, North Dakota State University, Fargo, ND 58108, USA. Electronic address: Sumit.Ghosh@ndsu.edu.
authors.forename: Sumit
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Veterinary and Microbiological Sciences, North Dakota State University, Fargo, ND 58108, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Hoselton
authors.affiliation: Department of Veterinary and Microbiological Sciences, North Dakota State University, Fargo, ND 58108, USA.
authors.forename: Glenn P
authors.initials: GP
authors.lastname: Dorsam
authors.affiliation: Department of Veterinary and Microbiological Sciences, North Dakota State University, Fargo, ND 58108, USA.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Schuh
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D001249:Asthma / Q000276:immunology*; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D008168:Lung / Q000276:immunology*; D010446:Peptide Fragments / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D010446:Peptide Fragments; D006820:Hyaluronic Acid
keywords: Asthma; Extracellular matrix; Hyaluronan