Hyaluronan (Hyaluronic Acid) in Bronchoalveolar Lavage Fluid during the Development of Bleomycin-induced Alveolitis in the Rat

Abstract

Hyaluronan (hyaluronate or hyaluronic acid) was measured in bronchoalveolar lavage (BAL) fluid from rats during a 30-day period after a single intratracheal dose of bleomycin. An increase of hyaluronan (HA) in BAL fluid was apparent by 3 days after bleomycin administration. Peak HA values were reached on Day 5 and were about 75 times higher than in control animals. Analyses of urea in BAL and HA in serum indicated that the increased levels of HA in BAL, postbleomycin, could not be explained by plasma leakage. The HA recovered by lavage decreased progressively after Day 5 and returned to normal 3 wk after bleomycin treatment. The HA content and an increased influx of PMN in BAL fluid were correlated and showed a similar time dependence, suggesting that enhanced synthesis of HA in the smaller airways is linked to the early inflammatory phase of the bleomycin injury.

Extracellular Superoxide Dismutase Inhibits Inflammation by Preventing Oxidative Fragmentation of Hyaluronan

“…Inflammatory injuries in the lung have also been shown to lead to an increase in hyaluronan in the BAL fluid (48,49). Savani et al (50) suggested that lung injury results in an increase in hyaluronan that, at least in part, mediates the inflammatory response to the injury.…”

Transactivation of Sphingosine 1-Phosphate Receptors Is Essential for Vascular Barrier Regulation

“…Studies utilizing HAS gene knock-out mice reveal that only HAS2 is required for viability with HAS2 deletion resulting in lethal abnormalities in cardiac development, which is rescued by addition of exogenous HA (9,10). Proinflammatory cytokines (TNF␣, IL-1␤) and LPS induce HA production in EC in vitro (11) and increased HA levels are observed in bronchoalveolar lavage fluid (BALF) from patients with inflammatory lung disorders such as pulmonary fibrosis, acute lung injury, and chronic obstructive pulmonary disease (12)(13)(14)(15). Further, intratracheal administration of nebulized high MW HA has been used to prevent injury in experimental emphysema (16).…”

“…Multiple CD44 isoforms result from extensive, alternative exon splicing events (23,24) with the alternative splicing often occurring between exons 5 and 15 leading to a tandem insertion of one or more variant exons (v1-v10, or exon 6 through exon 14) within the membrane proximal region of the extracellular domain (25,26). The variable primary amino acid sequence of different CD44 isoforms is further modified by extensive N-and O-glycosylations and glycosaminoglycan (GAG) additions (5,26).…”

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

“…During the experimental induction of bleomycin-induced alveolar injury in the rat there is a considerable accumulation of high molecular HYA in the oedematous interstitial alveolar space during the alveolitis phase [22,23,24], which has been attributed to alveolar interstitial fibroblast-like cells [24]. Experimental studies have also demonstrated a link between the alveolar and interstitial accumulation of HYA and the intraalveolar oedema and oedema of the fragile alveolar structure [25].…”