Cathepsin B and D activity in alveolar macrophages from rats with pulmonary granulomatous inflammation or acute lung injury

Cathepsin B and D activity was determined using specific synthetic substrates in alveolar macrophages (AMs) obtained from Sprague-Dawley rats with experimentally induced pulmonary granulomatous inflammation. Increased cathepsin B activity was found 4 days after intravenous injection of complete Freund's adjuvant (CFA), but not after injection of live bacillus Calmette-Guérin organisms (BCG), indicating that the enzyme response was unrelated to the subsequent development of granulomatous inflammation. Findings of comparable increases in enzyme activity following injection of mineral oil (MO) indicate that the response to CFA was due to the oil component. Significantly, oleic acid (OA), a natural fatty acid, did not stimulate enzyme activity although the agent, like MO, caused acute lung injury as assessed by 125I albumin uptake. At 7 and 28 days following injection of CFA, cathepsin B levels in AMs were the same as those in animals given normal saline (NS), although bronchoalveolar lavage (BAL) samples still contained increased numbers of AMs, and cells obtained at 28 days phagocytosed more polystyrene microspheres. Cathepsin D activity did not increase 4 days after injection of CFA or BCG + CFA; at 28 days following injection of BCG + CFA activity was significantly decreased as compared to animals given NS. The data reveal a differential response of two lysosomal enzymes during the early phases of granulomatous inflammation.