Accumulation of hyaluronan in bronchoalveolar lavage fluid is independent of iron-, complement- and granulocyte-depletion in bleomycin-induced alveolitis in the rat

Previous studies on bleomycin-induced alveolitis in rats have demonstrated a transient histological accumulation of hyaluronan (hyaluronate or hyaluronic acid) in the alveolar interstitium, corresponding to increases in hyaluronan (HA) levels in bronchoalveolar lavage (BAL) fluid and lung tissue extracts. The accumulation of HA was related to the influx of inflammatory cells, especially polymorphonucleated cells (PMNs) in BAL fluid and the increase in lung water. In this study we have investigated the influence of iron, complement and PMN dependent mechanisms on the early connective response of the lung in the bleomycin rat model. Iron depletion had no effect on HA or the cellular composition of lavage fluid recovered on day 4 post bleomycin. Treatment of bleomycin-injured rats with cobra venom factor (CVF), totally neutralized complement haemolytic activity but had no effect on lavage HA or the cell invasion in BAL. Treatment with anti-neutrophil serum (ANS), reduced blood and lavage PMN by 70-80%, but had no influence on HA levels in BAL. These results suggest that regulatory mechanisms other than those dependent on iron, complement activation or PMN recruitment are responsible for HA accumulation in this fibrosing alveolitis animal model.