Accumulation of Hyaluronic Acid in the Alveolar Interstitial Tissue in Bleomycin-induced Alveolitis

Abstract

By using biotin-labeled proteoglycan core protein and an avidin-enzyme system, hyaluronic acid (HA) was visualized in the lungs of rats at different times (4, 10, and 20 days) after bleomycin injury. Four days after an intratracheal injection of bleomycin, HA was accumulated in the edematous alveolar septa of the focal areas with lung tissue injury. An interstitial cellular infiltrate of mainly lymphocytes was present. In normal rat lung, HA was not seen in the alveolar tissue but confined to peribronchial and perivascular spaces. Ten and twenty days after bleomycin administration, increasing numbers of macrophages were apparent in the alveolar space. Proliferating fibroblasts and deposition of collagen in the alveolar tissue were observed while the diffuse HA accumulation was becoming less prominent in the alveolar interstitial tissue. HA was more distinctly located in the surroundings of proliferating fibroblasts. A few scattered alveolar macrophages showed a positive staining for HA. An increased water content of the lung was most apparent 4 days after bleomycin administration. The accumulation of HA, a glycosaminoglycan with unique qualities to immobilize water, in the alveolar interstitium suggests a role for HA in the alveolar interstitial edema. The appearance of HA in alveolar macrophages might indicate that macrophage phagocytosis contributes to the elimination of HA from inflamed lung tissue.

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].…”

Extracellular Superoxide Dismutase Inhibits Inflammation by Preventing Oxidative Fragmentation of Hyaluronan

“…Hyaluronan turnover and degradation increase during inflammation, and lower molecular mass species of hyaluronan accumulate. Importantly, this accumulation is detected prior to the influx of inflammatory cells and deposition of collagen, which suggests that low molecular mass hyaluronan accumulation is an early event in the development of inflammatory pulmonary disease (4). Although the mechanisms of hyaluronan turnover and degradation are still unknown, it is generally accepted that free radicals, especially the highly reactive hydroxyl radical, play an important role in the degradation process of hyaluronan (5,6).…”