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Lung Surfactant Alterations in Pulmonary Thromboembolism

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Lung Surfactant Alterations in Pulmonary Thromboembolism S. I-X, 1-284:Layout 1 24.11.2009 10:42 Uhr Seite 38 38 EUROPEAN JOURNAL OF MEDICAL RESEARCH December 7, 2009 Eur J Med Res (2009) 14(Suppl. IV): 38-41 © I. Holzapfel Publishers 2009 LUNG SURFACTANT ALTERATIONS IN PULMONARY THROMBOEMBOLISM A. Calkovska 1, D. Mokra 1, V. Calkovsk y2 1Department of Physiology, Jessenius Faculty of Medicine, Comenius University, Martin; 2Clinic of Otorhinolaryngology and Head and Neck Injury, Jessenius Faculty of Medicine, Comenius University, Martin and Martin Faculty Hospital, Slovakia Abstract cells or removed by macrophages from alveolar space. Beside neonatal respiratory distress syndrome, second - Life cycle of natural surfactant is controlled at local, ary surfactant deficiency may occur in patients with humoral and neural levels [1]. mature lungs. Recent studies revealed quantitative and By differential centrifugation two basic forms of qualitative changes of lung surfactant in pulmonary pulmonary surfactant were defined – large complexes thromboembolism (PTE) concerning the total phos - of active surfactant (large aggregates, LA) and small pholipids content in BAL fluid, alterations in surfac - inferior complexes (small aggregates, SA). A decrease tant phospholipids classes and a large-to-small aggre - in the large-to-small aggregates ratio is one of the gates ratio. Reduced expression of surfactant protein markers of lung injury [2]. This review will focus on A (SP-A) mRNA and SP-A in lung tissue after pul - changes of pulmonary surfactant system that occur in monary embolism was found. Serum levels of SP-A pulmonary thromboembolism. were significantly higher in patients with PTE than in other lung diseases, except COPD. Surfactant changes HISTORY in PTE may result from damage of type II cells by hy - poxia, leakage of plasma proteins into the airspaces First documented study designed to give an evidence and/or by reactive oxygen species. They can con - of relationship between pulmonary circulation and tribute to lung atelectasis and edema, and a further re - surfactant was performed by Finley et al [3]. Occlusion duction in oxygen saturation as seen in clinical picture of pulmonary artery in dogs during two hours led to of PTE. Surfactant changes are reliable marker of reduction in surfactant activity lasting for six weeks. lung injury that might become a prognostic indicator Sutnick and Soloff [4] examined post mortem surface in patients with pulmonary thromboembolism. activity in saline extracts of human lungs involved with emboli. The investigation revealed increased min - Key words: pulmonary surfactant; inactivation; throm - imal surface tension indicating a severe surfactant ab - boembolism; SP-A normality. Incorporation of 14 C-palmitate into phos - pholipids by lung slices was also markedly impaired by INTRODUCTION embolism. These findings support the concept that obstruction to the pulmonary circulation interferes Pulmonary surfactant is a lipoprotein complex that with surfactant production; thus contributing to at - covers the inner surface of the lungs. It prevents col - electasis seen in pulmonary embolism. Some years lat - lapse of the alveoli and small airways during expiration er, bromhexine, known as a stimulator of surfactant by reducing surface tension at the air-liquid interface synthesis and secretion, had protective effect on the and allows efficient gas exchange at low transpul - acute impairment of pulmonary function due to mi - monary pressures. It is composed of several phospho - crothrombosis in rabbits [5]. Surfactant replacement lipids, neutral lipids and surfactant specific proteins. therapy in two patients with suspect pulmonary em - The largest proportion of phospholipids is phos - bolism was documented in 1991 [6]. Two adolescents phatidylcholine, of which dipalmitoylphosphatidyl - (12 and 16 years old) with acute leukemia and severe choline (DPPC) is the major surface-active compo - respiratory failure due to leukemia treatment were giv - nent. Four native surfactant proteins have been identi - en the modified natural surfactant Curosurf. Surfac - fied. The hydrophobic surfactant proteins B (SP-B) tant administration improved ventilation and oxygena - and C (SP-C) are thought to be important for the sur - tion and made confirmation of the diagnosis possible. face-tension lowering properties of pulmonary surfac - All these results probably formed a background for tant. Surfactant proteins A (SP-A) and D (SP-D) are later clinical studies demonstrating a tight relation be - hydrophilic and they play a role in surfactant metabo - tween surfactant and pulmonary embolism. lism and in pulmonary host defence [for review, see 1]. Surfactant is produced by alveolar type II cells, LUNG SURFACTANT IN PULMONARY where it is stored in intracellular vesicles termed lamel - THROMBOEMBOLISM lar bodies. After secretion into the alveolar surface it forms tubular myelin and further spreads to a thin Surfactant deficiency has been recognized as the cause film. “Consumed” surfactant is recycled by type II of respiratory distress syndrome (RDS) in premature S. I-X, 1-284:Layout 1 24.11.2009 10:42 Uhr Seite 39 December 7, 2009 EUROPEAN JOURNAL OF MEDICAL RESEARCH 39 infants. However, secondary surfactant deficiency re - nificantly higher in current smokers than in never- or sulting from inactivation of surfactant system may oc - ex-smokers, and it was also higher in patients with cur in patients with mature lungs. Nowadays, there is a COPD and pulmonary thromboembolism than in oth - growing body of evidence on qualitative and quantita - er diseases. In thromboembolism, higher serum levels tive changes of lung surfactant in pulmonary throm - of SP-A may be explained by increased permeability boembolism (PTE) [7]. PTE induced an increase in of alveolar-capillary barrier due to alveolar ischemia, the total phospholipid content in bronchoalveolar and epithelial and endothelial damage, enabling SP-A lavage (BAL) fluid on the first day and decrease on the to leak into the circulation [13]. It suggests that serum tenth day after the diagnosis of PTE in comparison to SP-A may represent a useful and valuable marker in di - control patients without cardiorespiratory disease. Al - agnostics of pulmonary thromboembolism and assess - terations in surfactant phospholipids classes were also ment of treatment efficiency. observed. On the first day of the disease, relative amounts of phosphatidylcholine (PC) and phospha- MECHANISMS OF SURFACTANT ALTERATIONS tidylglycerol (PG) decreased and sphingomyelin (SM), phosphatidylinositol (PI) and lysophosphatidylcholine The degree of surfactant inactivation depends on the (Lyso-PC) increased. Concentration of PC, SM and PI extent of pulmonary embolism, and it is supposed to did not change significantly in the course of disease. be larger in acute massive forms of PTE accompanied Another important finding is a change in the surfac - by severe hypoxia and metabolic acidosis. Even tant large-to-small aggregates ratio. In patients with though the complex mechanism of pulmonary surfac - PTE, the abundance of large active aggregates (LA) in tant injury in PTE is not fully elucidated, several fac - bronchoalveolar lavage fluid falls in favor of small ag - tors may be defined (Fig. 1). An increase in the total gregates (SA) with low surface activity. The rise in SA phospholipids amount shortly after the onset of PTE is supposed to be responsible for an increase in ab - can be attributed to enhanced synthesis and/or secre - solute value of phospholipids on the first day of PTE, tion, perturbation of phospholipids reuptake by alveo - as this finding correlates with reduction of surfactant lar type II cells, or by release of phospholipids from biophysical activity in PTE patients [7]. damaged cell membranes. As hyperventilation was shown to have stimulatory effect on surfactant synthe - SURFACTANT -S PECIFIC PROTEIN A (SP-A) sis and secretion [14], another proposed mechanism is a change in breathing pattern which typically occurs in As mentioned above, the protein components consti - patients with PTE and may promote phospholipids tute approximately 10% by weight of pulmonary sur - changes. Phospholipid production may be enhanced factant, half of which consists of four surfactant-as - also by activation of both parts of autonomic nervous sociated proteins A, B, C and D. Among them, SP-A is system, sympathetic and parasympathetic [15], and by most abundant pulmonary surfactant protein that be - hormonal stimulation. longs to the family of innate host defense proteins A late decrease in the total phospholipids in the termed collectins [8]. Beside pulmonary host defense, course of the PTE could reflect type II cell injury as a SP-A is also involved in the formation of pulmonary result of hypoperfusion and hypoxia, or inflammation. surfactant, as it is essential for the structure of tubular Special role is probably played by lysophosphatidyl - myelin. The levels of SP-A are decreased in the lungs choline that is generated by phospholipids subjected of patients with cystic fibrosis, respiratory distress to phospholipase A 2 hydrolysis. Its amount increases syndrome, pneumonia and another chronic lung dis - soon after PTE and can significantly affect surface eases [8, 9]. tension [7]. Another reason of the decrease in phos - Apart from phospholipids changes, reduced expres - pholipids content later on may be depletion of intra - sion of SP-A mRNA and SP-A in lung tissue after cellular sources of surfactant and/or enhancement of pulmonary embolism was found [10].
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