Pneumoproteinaemia: a new perspective in the assessment of lung disorders

Abstract

The glomerular and alveolar capillary walls share several features in their structure and function. Both consist of endothelial and epithelial layers resting on their respective basal membrane. A basic common requirement for an appropriate functioning of these barriers is that they should allow a free diffusion and/or filtration of small molecules (solutes and gases) but efficiently retain larger plasma proteins. The functional capacity of these barriers mainly depends on their available exchange/filtration surface area which can be evaluated by the diffusion capacity of the lung for carbon monoxide (DL,CO) and the glomerular filtration rate (GFR) for the kidney.Retention of plasma proteins at the level of the kidney is achieved by the glomerular filter whose polyanionic and porous properties almost completely hinder the filtration of negatively-charged proteins the size of albumin or larger. The selectivity of this filtration process is also dependent upon the glomerular haemodynamics i.e., the GFR and its determinants. By contrast, the glomerulus allows a free filtration of small molecules including the low molecular weight (LMW) proteins (<40 kDa) which are reabsorbed and catabolized by the proximal tubule. Loss of glomerular permselectivity results in an increased excretion of albumin and other high molecular weight proteins (glomerular proteinuria), which is an important hallmark of glomerular diseases, whereas impairment of tubular funtion is associated with an increased excretion of LMW proteins (tubular proteinuria) [1]. With respect to the lung, there is increasing evidence that, as in the kidney, the transepithelial passage of proteins is governed by steric, electrostatic and haemodynamic factors. Human and animal studies have indeed shown that the ability of proteins and tracers to move across the lung epithelium/blood barrier is inversely proportional to their molecular size and influenced by their shape [2,3,4]. This was demonstrated not only for the penetration of plasma proteins into the lung but also for the clearance of proteins and tracers from the alveolar spaces [4]. In the lung as opposed to the kidney, the flux of proteins across the epithelial barrier is however bidirectional. The predominant route of this passage appears to be paracellular via tight junctions between epithelial cells. Transcellular transport has been reported but appears to be of minor importance [4]. As for the kidney, heteroporous models have been proposed for the lung epithelium/blood barrier with a predominant population of small por-es and a small fraction of much larger pores. There is no general agreement about the exact permeability of this barrier and pore-size estimates vary between 0.5-2.5 nm for the small pores and up to 400 nm for the larger ones [2,5,6]. In addition to size-selective properties, polyanionic proteoglycans are present on the capillary and epithelial basal membranes as well as the interstitium, which generate an electric field repelling negatively-charged macromolecules [7,8]. The leakage of pr...

Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis

“…The lack of correlation between CC16 in serum and albumin in BALF is not inconsistent with that hypothesis, since these proteins show substantial differences with respect not only to their sizes, but also their directions, routes and mechanisms of passage across the air-blood barrier. Although little is known about their exact routes and sites of passage, proteins moving across the air-blood barrier have to be transferred across the epithelial and the endothelial layers, their respective basal membranes, as well as the interstitium [11,12,32]. Several lines of evidence suggest that proteins cross the air-blood barrier paracellularly, through water-filled pores located at the junctional complexes linking epithelial and endothelial cells [33].…”

“…According to recent human and experimental studies, the integrity of the air-blood barrier and its permeability to macromolecules might be assessed less invasively by the quantification, in serum, of lung-specific secretory proteins, also referred to as "pneumoproteins" [11,12]. One of these proteins is the Clara cell secretory protein, a low-molecular-weight protein of 16 kDa (CC16), secreted in large amounts into the lumen of the respiratory tract by nonciliated bronchiolar Clara cells [13,14].…”

Swimming pool, respiratory health, and childhood asthma: Should we change our beliefs?

“…1 In fact, the serum levels of the pneumoproteins SP-A, SP-B, and CC16 reflect the permeability and/or cellular integrity of the pulmonary epithelium. [38][39][40] Bernard et al 1 found that the regular attendance of an indoor chlorinated pool was the main factor affecting lung epithelium of children, with a positive dose-effect relationship between cumulated pool attendance and serum SP-A and SP-B levels. CC16 was also positively associated with cumulated pool attendance, but no clear dose-effect relationship emerged.…”

Exposure to trichloramine and respiratory symptoms in indoor swimming pool workers

“…A study among Belgian schoolchildren claimed that visiting chlorinated pools was strongly related to the prevalence of asthma and positive exercise-induced bronchoconstriction [7]. Furthermore, a positive dose-effect relationship was found between pool attendance in adults and children and serum surfactant protein-A and -B, which are markers of lung epithelium hyperpermeability in a variety of acute or chronic lung disorders [8,9]. However, as swimming is often considered healthy for asthmatics, especially for children, asthma-related referral to improve their general condition might play a role in exacerbating their symptoms and the meaning of changes in biomarker levels is unclear [6].…”