Lung accumulation of hyaluronan parallels pulmonary edema in experimental alveolitis

Abstract

The glycosaminoglycan hyaluronan (HA, hyaluronate or hyaluronic acid) was quantified in rat lung during the development of bleomycin-induced lung injury. Extracted lung HA was measured by a radiometric assay. In control rats, the HA lung content was 95 +/- 5 (SE) micrograms/g of freeze-dried and homogenized lung tissue. After a single intratracheal instillation of bleomycin, the HA content of the lung increased significantly on day 1. Peak HA concentrations on days 3-7 averaged 70% higher than normal lung HA concentrations. From day 7 the HA concentrations progressively declined and had returned to normal by day 30. Qualitative assessment of lung HA has previously demonstrated that HA is accumulated in the edematous interstitial alveolar space during the alveolitis phase of bleomycin injury. Since high-molecular-weight HA has unique hydrophilic properties, another aim of the study was to elucidate the possible link between the increase in lung HA and the development of interstitial-alveolar edema postbleomycin. HA recovered by bronchoalveolar lavage from bleomycin-injured lungs increased with increasing total lung HA and had a mean molecular size of 220,000 +/- 50,000 (SE), indicating the minimum size of HA accumulated in the alveolar space. The relative lung water increased significantly on days 3-7 after bleomycin administration. A close relationship (P less than 0.001) and time dependence between the increase in relative lung water and the increase in lung HA were found.

Lung Water and Proton Magnetic Resonance Relaxation in Preterm and Term Rabbit Pups: Their Relation to Tissue Hyaluronan

“…Hällgren et al (30) observed accumulation of HA in the small airways in patients with adult respiratory distress syndrome and proposed that it contributed to water immobilization and generation of interstitial and alveolar edema. In agreement with this contention, a strong positive correlation has been reported between tissue HA and the water content of the lung (31,32).…”

Hyaluronan turnover in relation to infection and sepsis

“…In human ARDS increased concentrations of hyaluronan in bronchoalveolar lavage fluid (BAL) has been found [27], and in a porcine model of sepsis-induced lung injury resembling ARDS, accumulation of interstitial hyaluronan has been seen [19]. This is in analogy to the increased amounts of hyaluronan found both interstitially and in BAL fluid in other interstitial inflammatory pulmonary diseases such as sarcoidosis and allergic alveolitis [28,29,30]. Possibly, more knowledge of the changes in pulmonary interstitial hyaluronan metabolism in relation to sepsis may provide new information on the pathophysiology of ARDS development.…”

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]. The hypothesis that interstitial water trapped by HYA may result in impaired lung function is further supported by the clinical observations of a close relationship between high amounts of HYA recovered by BAL and reduced gas diffusion of the lung in patients with acute farmer's lung [20] or adult respiratory distress syndrome [26].…”