Surfactant protein-A (SP-A) leaks into the circulation of patients with acute respiratory distress syndrome (ARDS) or acute cardiogenic pulmonary edema (APE) in a manner inversely related to lung function. Since surfactant protein-B (SP-B) is synthesized as a precursor considerably smaller than alveolar SP-A, we investigated whether it enters the circulation more readily. Reactivities consistent with SP-B proprotein (approximately 42 to approximately 45 kD) and the approximately 25 kD processing intermediate were detected in plasma. Plasma immunoreactive SP-B levels were significantly higher in ARDS (8,007+/-1,654 ng/ml [mean+/-SEM], n = 22) and APE (3,646+/-635 ng/ml, n = 10) patients compared with normal subjects (1,685+/-58 ng/ml, n = 33) and ventilated patients with no cardiorespiratory disease (1,829+/-184 ng/ml, n = 7). All groups had plasma SP-B/SP-A ratios approximately 6- to approximately 8-fold higher than in normal lavage or ARDS tracheal aspirate fluid, consistent with protein sieving. During admission, both plasma SP-B and the SP-B/SP-A ratio were inversely related to blood oxygenation (PaO2/FIO2) (p < 0.0001 and p < 0.025, n = 260 from 39 patients; Spearman) and static respiratory system compliance (deltaV/deltaP) (p < 0.0001 and p < 0.01, n = 168 from 25 patients). We describe in detail three patients and conclude that immunoreactive SP-B enters more readily than SP-A, is cleared acutely, and provides a better indicator of lung trauma.

Detection of alveolo-capillary damage has important implications for treatment modalities in ventilated patients. Although surfactant protein-A (SP-A) is normally only found in appreciable amounts in the lung, we describe significantly elevated concentrations in the sera of patients with acute cardiogenic pulmonary edema (median, 250 ng/ml; range, 180 to 364; n = 10) and in those with the adult respiratory distress syndrome (ARDS) (median, 378 ng/ml; range, 215 to 1,378; n = 15) relative to healthy control subjects (median, 175 ng/ml; range, 123 to 248; n = 15) and ventilated patients with no cardiorespiratory disease (median, 169 ng/ml; range, 126 to 253; n = 6) (p < 0.01, in all cases). Serum SP-A was inversely related to blood oxygenation and to static respiratory system compliance both at the time of the patient's entry into the study (p < 0.005, rs = -0.51, n = 31; p < 0.001, rs = 0.82, n = 17; respectively) and during the course of admission (p < 0.001, rs = -0.34, n = 168; p < 0.001, rs = -0.50, n = 111; respectively). In addition, we describe in detail three cases of ARDS where lung function either improved, remained static, or deteriorated. We conclude that serum SP-A is an acute indicator of lung function and alveolo-capillary membrane injury.

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We examined the effects of short-term cyclic stretch on both phosphatidylcholine (PC) secretion and apoptosis in primary cultures of rat alveolar type II cells. A 22% cyclic stretch (3 cycles/min) was applied to type II cells cultured on silastic membranes using a Flexercell strain unit. This induced, after a lag period of about 1 h, a small, but significant release of [ Q H]PC from prelabelled cells. In addition, stretch increased nuclear condensation, the generation of oligosomal DNA fragments and the activation of caspases. Similar responses were triggered by sorbitol-induced osmotic shock, but not by the secretagogue ATP. We conclude that stretch can induce both apoptosis and PC secretion in alveolar type II cells and propose that these diverse responses occur within the lung as a consequence of normal respiratory distortion of the alveolar epithelium.z 1999 Federation of European Biochemical Societies.

Surfactant proteins A and B (SP-A and SP-B) enter the circulation in a manner that acutely reflects changes in pulmonary function in patients with acute respiratory failure (ARF). There is a small but significant gradient in SP-A and SP-B from arterial to mixed venous (A-V) blood, and since we have detected both proteins in urine, the kidney may be a major site of their systemic clearance. Clara cell secretory protein 16 (CC16), which leaks from the respiratory tract, is known to be freely eliminated by the kidney. Lung plasma protein levels will depend on the rates of both protein entry into and clearance from plasma. In order to study the limiting variable determining these levels, we compared plasma CC16, SP-A, and SP-B in matching A-V blood samples from 37 ARF patients with indices of lung dysfunction and glomerular filtration rate (GFR) (of plasma cystatin C and creatinine). Cystatin C, CC16, SP-A, and SP-B were reduced in mixed venous plasma (all p < 0.001) and their A-V gradients were directly related to their arterial levels (all p < 0.03). Whereas CC16, SP-A, and SP-B reflected blood oxygenation (all p < 0.05), only SP-A and SP-B were related to lung injury score (LIS) (both p < 0.05). In contrast, whereas the clearances of both CC16 and cystatin C were related to that of creatinine (p < 0.02 for both), the clearances of SP-A and SP-B were not. Our study confirms that all three lung proteins are acutely cleared from the circulation of patients with ARF (half-lives < 18 min), and we conclude that whereas the plasma concentration of CC16 depends on GFR, plasma concentrations of SP-A and SP-B reflect lung function independently of this variable.