Effects of elastase and cigarette smoke on alveolar epithelial permeability

To determine whether instilled porcine pancreatic elastase (PPE) increases alveolar epithelial permeability, we measured alveolar epithelium permeability x surface area (PS) for [¹⁴C]sucrose and ¹²⁵I-bovine serum albumin (¹²⁵I-BSA) in isolated perfused lungs from hamsters previously exposed to PPE and/or cigarette smoke. Saline (0.5 ml) with 0, 5, or 20 units PPE was instilled intratracheally in anesthesized hamsters. Those exposed to smoke for 4-6 wk received 0 or 5 units; PS was measured 3 h later. Nonsmokers received 0, 5, or 20 units; PS was measured 3 h, 24 h, or 5 days later. Control PS values were (cm³/s x 10^-4, ±SE) 0.84 ± 0.11 for sucrose and 0.030 ± 0.006 for BSA. Three and 24 h following 20 units PPE, (PS)(sucrose) was twice the control valve. (PS)(bsa) was four times control at 3 h but not significantly increased at 24 h. Five days after PPE both were back to control levels. Five units PPE or smoke exposure alone caused no PS changes. Smoke exposure and 5 units PPE caused (PS)(sucrose) to increase markedly (1.85 ± 0.32); (PS)(bsa) was not significantly increased (0.076 ± 0.026). Thus instilled PPE causes reversible increases in alveolar epithelial PS; cigarette smoking potentiates this effect.