Measurement of ceruloplasmin in the lungs of patients with acute respiratory distress syndrome: Is plasma or local production the major source?

Background: Oxidant-induced tissue damage is thought to contribute to the l ung injury seen in patients with acute respiratory distress syndrome (ARDS) . Ceruloplasmin (CP) is a major circulating antioxidant increased levels of which have been measured in bronchoalveolar lavage fluid (BALF) taken from such patients. Traditionally, CP detected in these circumstances was thoug ht to be plasma-derived, moving into the alveolar spaces as a consequence o f the increased alveolar-capillary permeability that characterises ARDS. Ho wever, recent studies in murine models suggest that CP may be synthesised i n the airways and even alveoli under physiological conditions. Objectives: The aims of this investigation were therefore to identify the source of any increased levels of CP detectable in BALF taken from patients with establi shed ARDS. Methods: Matched BALF and plasma samples taken from patients wit h ARDS (n = 46) and from controls without lung disease (n = Il)were analyse d for CP (132 kD) and plasma specific albumin (ALB, 68 kD) and (alpha (2)-m acroglobulin (alpha (2)-M, 820 kD). Results: All three proteins were increa sed in BALF taken from patients with ARDS compared to controls (p < 0.01, A LE and CP; p < 0.001, alpha (2)-M). When protein levels were expressed as t he ratios of BALF: plasma (designated Q), Q(CP) and Q(alpha2)-M increased i n parallel to Q(ALB) (P < 0.001), indicating that all increases were primar ily plasma-derived. Their relative coefficients of excretion (RCE: Q(CP)/Q( ALB) and Q(<alpha>2-M)/Q(ALB)) demonstrated that the larger molecular weigh t protein, alpha (2)-M, gave the best discrimination between patients with ARDS and normal controls (0.85 vs. 0.04; p < 0.01), indicating that this wa s the most sensitive marker of alveolar-capillary permeability. Conclusions : Increased levels of CP in BALF from patients with ARDS are mainly attribu table to plasma exudation. Copyright (C) 2000 S. Karger AG, Basel.