title: Hyaluronan stimulates ex vivo B lymphocyte chemotaxis and cytokine production in a murine model of fungal allergic asthma.
abstract: Allergic asthma is a chronic inflammatory disease of the airways characterized by excessive eosinophilic and lymphocytic inflammation with associated changes in the extracellular matrix (ECM) resulting in airway wall remodeling. Hyaluronan (HA) is a nonsulfated glycosaminoglycan ECM component that functions as a structural cushion in its high molecular mass (HMM) but has been implicated in metastasis and other disease processes when it is degraded to smaller fragments. However, relatively little is known about the role HA in mediating inflammatory responses in allergy and asthma. In the present study, we used a murine Aspergillus fumigatus inhalational model to mimic human disease. After observing in vivo that a robust B cell recruitment followed a massive eosinophilic egress to the lumen of the allergic lung and corresponded with the detection of low molecular mass HA (LMM HA), we examined the effect of HA on B cell chemotaxis and cytokine production in the ex vivo studies. We found that LMM HA functioned through a CD44-mediated mechanism to elicit chemotaxis of B lymphocytes, while high molecular mass HA (HMM HA) had little effect. LMM HA, but not HMM HA, also elicited the production of IL-10 and TGF-β1 in these cells. Taken together, these findings demonstrate a critical role for ECM components in mediating leukocyte migration and function which are critical to the maintenance of allergic inflammatory responses.
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: Steve B
authors.initials: SB
authors.lastname: Wanjara
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Carlson
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: McCarthy
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: D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000382:microbiology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000276:immunology; D005260:Female; D018960:Hyaluronan Receptors / Q000276:immunology; D006820:Hyaluronic Acid / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis
chemical_list: D000946:Antigens, Fungal; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; C556062:IL10 protein, mouse; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D007073:Immunoglobulin E; D006820:Hyaluronic Acid
keywords: Aspergillus fumigatus; B lymphocytes; Hyaluronan