Increase of C-Reactive Protein and Decrease of Surfactant Protein A in Surfactant after Lung Transplantation

Abstract

In this study, we asked whether the serum acute-phase protein C-reactive protein (CRP) increased in large surfactant aggregates after lung transplantation and analyzed the changes in composition and interfacial adsorption activity of those aggregates. Single left lung transplantation was performed in weight-matched pairs of dogs. A double-lung block from the donor animal was flushed with either modified Euro-Collins solution (EC) (n = 6) or University of Wisconsin solution (UW) (n = 6) at 4 degrees C followed by immersion in cold EC or UW for 22 h. The left donor lung was transplanted. The recipient dog was then reperfused for 4.5 h. Irrespective of the preservation fluid, gas exchanged was impaired in the transplanted lung after 4.5 h of reperfusion. Large surfactant aggregates obtained from this lung showed reduced ability to rapidly adsorb to an air-liquid interface. Phospholipid (PL) content and PL composition of surfactant from lung transplants was similar to that of the control lungs. However, the content of surfactant protein A decreased after reperfusion. In addition, Western blot analyses showed that levels of CRP increased in surfactant from transplanted but not from donor lungs. The addition of human CRP to control surfactant (CRP:PL weight ratio, 0.01:1) caused a decrease of surfactant adsorption. We conclude that the impairment of adsorption facilities of surfactant from transplanted lungs may be correlated with decreased levels of surfactant protein A and increased levels of CRP. The presence of elevated levels of CRP in bronchoalveolar lavage could be a very sensitive marker of lung injury.

High-throughput evaluation of pulmonary surfactant adsorption and surface film formation

“…Deactivation of surfactant by serum components and by inflammatory mediators leaked into the alveolar spaces is thought to be a major determinant of the respiratory failure in acute respiratory distress associated with lung injury (16,47). The surface-inhibitory activity of proteins such as albumin (8,48), fibrinogen (49), C-reactive protein (9,50), or lipases (51) toward surfactant has been well documented, as well as the deactivating effect of metabolites such as neutral lipids (46,52), FFAs (53), bile salts (54), heme derivatives (55), or lysophospholipids (33,53). Lung injury with different sources and to different extents is probably associated with particular complex and possibly multifactorial profiles of surfactant deactivation that have been only preliminarly characterized.…”

“…In particular, accidental aspirates (e.g., meconium, hydrochloric acid), airborne particles (e.g., bacteria, pollen, dust), toxins, vapors, organic molecules derived from combustion, and ozone and other environmental pollutants can reach the most distal parts of the respiratory tract and contribute, to a variable extent, to surfactant inactivation. Additionally, the surfactant system can be further damaged by substances leaking through the capillary-epithelial barrier [in particular plasma proteins such as albumin (8) or the C-reactive protein (9)] in response to acute lung injury, usually associated with pro-inflammatory processes (10,11).…”

Physical properties and surface activity of surfactant‐like membranes containing the cationic and hydrophobic peptide KL4

“…The ability of the lipid mixtures to absorb onto and spread at the air-water interface was tested in the absence and presence of KL 4 , at 25 and 37°C, in a Wilhelmy-like high sensitive surface microbalance [36,43]. The samples were injected into the hypophase chamber of the Teflon dish, which contained 6 mL of 5 mm Hepes buffer, pH 7.0, 150 mm NaCl, either with or without 5 mm CaCl 2 , with continuous stirring.…”

Beneficial effects of synthetic KL4surfactant in experimental lung transplantation

“…Single left lung transplantation procedures were performed in weight-matched pairs of large (17-23 kg) Landrace 6 Large White pigs, as described previously [5,7]. A total of 28 pigs was divided randomly into two groups: 1) an untreated group (n512; six donors and six recipients) and 2) a KL 4 O, the trachea stapled and the heart-lung block stored at 4uC for 22 h. Recipients underwent a left posterolateral thoracotomy and the left lung was clamped, excised and lavaged ex situ.…”

“…Inflammatory mediators released by resident donor macrophages, and recruitment and activation of circulating recipient neutrophils are believed to play a significant role in the cascade of events leading to lung dysfunction [2]. Alteration of the alveolar surfactant system is another important factor contributing to lung dysfunction after lung transplantation during the early reperfusion period [3][4][5][6][7].…”