Hyaluronan deposition and correlation with inflammation in a murine ovalbumin model of asthma

Abstract

Asthma is a chronic inflammatory disease of the airways characterized by airway remodeling, which includes changes in the extracellular matrix (ECM). However the role of the ECM in mediating these changes is poorly understood. Hyaluronan (HA), a major component of the ECM, has been implicated in asthma as well as in many other biological processes. Our study investigates the processes involved in HA synthesis, deposition, localization and degradation during an acute and chronic murine model of ovalbumin (OVA)-induced allergic pulmonary inflammation. Mice were sensitized, challenged to OVA and sacrificed at various time points during an 8-week challenge protocol. Bronchoalveolar lavage (BAL) fluids, blood, and lung tissue were collected for study. RNA, HA, protein and histopathology were analyzed. Analyses of lung sections and BAL fluids revealed an early deposition and an increase in HA levels within 24 hours of antigen exposure. HA levels peaked at day 8 in BAL, while inflammatory cell recovery peaked at day 6. Hyaluronan synthase (HAS)1 and HAS2 on RNA levels peaked within 2 hours of antigen exposure, while hyaluronidase (HYAL)1 and HYAL2 on RNA levels decreased. Both inflammatory cell infiltrates and collagen deposition co-localized with HA deposition within the lungs. These data support a role for HA in the pathogenesis of inflammation and airway remodeling in a murine model of asthma. HA deposition appears largely due to up regulation of HAS1 and HAS2. In addition, HA appears to provide the scaffolding for inflammatory cell accumulation as well as for new collagen synthesis and deposition.

Inhibition of hyaluronan synthesis restores immune tolerance during autoimmune insulitis

“…HA content was likewise reduced in isolated islets that were cultured overnight in 4-MU ( Figure 4F). These data are consistent with the established role of 4-MU as an inhibitor of HA synthesis in other tissues (19,20).…”

TSG-6 Protein Is Crucial for the Development of Pulmonary Hyaluronan Deposition, Eosinophilia, and Airway Hyperresponsiveness in a Murine Model of Asthma

“…TSG-6 Deficiency Results in Reduced Pulmonary HA Deposition-We have recently described the temporal association between pulmonary HA deposition and eosinophilia during the induction and propagation of acute and chronic antigen-induced pulmonary inflammation and found that the maximum HA lung deposition and eosinophilia occur at around day 6 (45). Additionally, in our accompanying article (59), we show that TSG-6 enhanced HA accumulation and leukocyte binding in an in vitro model of HA synthesis.…”

Hyaluronan and Its Heavy Chain Modification in Asthma Severity and Experimental Asthma Exacerbation

“…In asthma, studies have linked HA levels in the bronchoalveolar lavage fluid (BAL) with inflammation and have been shown to increase after histamine challenge (4,5). Our published data in a mouse model of asthma revealed increased HA in BAL of mice during the course of inflammatory cell recruitment (6,7). Increased HA deposition was detected in the peribronchioles and perivascular regions in the lung.…”