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

Abstract

Background: TSG-6 is important in the organization of hyaluronan (HA). Results: Lack of TSG-6 results in diminished HA accumulation, inflammation, and airway hyperresponsiveness. Conclusion: TSG-6 is essential for the pathological manifestations in a murine model of asthma. Significance: TSG-6 is likely to contribute to the pathogenesis of asthma.

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

“…The present data indicate that the formation of HC-HA in asthmatic airways may contribute to exacerbations associated with asthma, and our previous mouse data further support this conclusion (14). We have previously demonstrated that mice lacking the ability to form HC-HA (TSG-6 Ϫ/Ϫ ) develop less inflammation and lower airway hyperresponsiveness and accumulate less HA in their airways after allergen challenge in a model of allergic asthma (14). The mechanism whereby HC-HA directs inflammatory events in asthma is not fully known, but it is likely to involve the increased avidity of leukocytes to HC-HA matrices rather than to HA alone (12,13).…”

“…a milder form of exacerbations associated with asthma identified the formation of HC-HA matrices as a therapeutic target for the treatment of asthma (14). The present manuscript supports these observations in human asthmatic tissue, BAL, and serum, linking the accumulation of HA and HC-HA to asthma severity and providing further evidence for their role in the pathogenesis of this disease.…”

“…The authors declare that they have no conflict of interest with the contents of this article. 1 lower airway hyperresponsiveness (14). Additionally, Liang et al (15) published data indicating deranged HA homeostasis in asthma with an increased HA production by human asthmatic airway fibroblasts.…”

Eosinophil Peroxidase Catalyzed Protein Carbamylation Participates in Asthma

“…Airway hyperresponsiveness and lung mechanics were measured in mice (n ϭ 9 per group) in response to increasing doses of inhaled methacholine as described (85). Mice were anesthetized with an i.p.…”

Hyaluronan mediates ozone-induced airway hyperresponsiveness in mice.

“…Exposure to ozone was independently shown to fragment hyaluronan from HMW-HA to sHA (6). Furthermore, studies of murine asthma show that TSG-6, which links hyaluronan to I␣I, is necessary for the development of inflammatory AHR (7). Finally, CD44 is necessary for the development of sHA-induced AHR in a tracheal ring model (2).…”