Amyloid associated with elastin-staining laminar aggregates in the lungs of patients diagnosed with acute respiratory distress syndrome

Abstract

BackgroundThe heterogeneity of conditions underlying respiratory distress, whether classified clinically as acute lung injury (ALI) or the more severe acute respiratory distress syndrome (ARDS), has hampered efforts to identify and more successfully treat these patients. Examination of postmortem lungs among cases clinically diagnosed as ARDS identified a cohort that showed a consistent morphology at the light and electron microscope levels, and featured pathognomonic structures which we termed elastin-staining laminar structures (ELS).MethodsPostmortem tissues were stained using the Verhoeff-Van Gieson procedure for elastic fibers, and with Congo red for examination under a polarizing microscope. Similar samples were examined by transmission EM.ResultsThe pathognomonic ELS presented as ordered molecular aggregates when stained using the Verhoeff-van Gieson technique for elastic fibers. In several postmortem lungs, the ELS also displayed apple-green birefringence after staining with Congo red, suggesting the presence of amyloid. Remarkably, most of the postmortem lungs with ELS exhibited no significant acute inflammatory cellular response such as neutrophilic reaction, and little evidence of widespread edema except for focal intra-alveolar hemorrhage.ConclusionsPostmortem lungs that exhibit the ELS constitute a morphologically-identifiable subgroup of ARDS cases. The ordered nature of the ELS, as indicated by both elastin and amyloid stains, together with little morphological evidence of inflammation or edema, suggests that this cohort of ARDS may represent another form of conformational disease. If this hypothesis is confirmed, it will require a new approach in the diagnosis and treatment of patients who exhibit this form of acute lung injury.

Supramolecular Amyloid-like Assembly of the Polypeptide Sequence Coded by Exon 30 of Human Tropoelastin

“…In the latter case, the elastotic material was shown to contain amyloid-like fibers (60). Furthermore, it is also known (61) that the degradation of human tropoelastin by elastase is strongly enhanced by the presence of unsaturated fatty acids, the same lipids found to accumulate on elastic fibers in atheromathous plaques.…”

Conformational and thermal characterization of a synthetic peptidic fragment inspired from human tropoelastin: Signature of the amyloid fibers

“…Elastin, the protein responsible for elasticity of tissues, such as lung, skin and arterial walls consists of a three-dimensional network whose turnover is almost absent under physiological conditions. However, under pathological conditions, the elastolysis by matrix metalloproteinase-12 (MMP-12) can produce biological active fragments as it was shown in photo-damaged skin [1], arteries of atherosclerotic patients [2] and in lung where the elastotic material contains amyloid-like fibres [3].…”

Elastin peptides in aging and pathological conditions

“…As a matter of fact, they demonstrated that the polypeptide sequence encoded by exon 30 (EX30) of the human tropoelastin gene was able to give rise to amyloid-like fibers in vitro (48) . Indeed, they suggested that the increased presence of elastase activities with age could accelerate the degradation of elastin by elastases, generating some elastin fragments with amyloidogenic properties (49) . Interestingly, several reports have evidenced the presence of deposits containing elastin fragments, called elastotic material, in photodamaged skin, in atheromatous plaques, and in lung alveolae of patients with acute interstitial lung disease (49) .…”

“…Indeed, they suggested that the increased presence of elastase activities with age could accelerate the degradation of elastin by elastases, generating some elastin fragments with amyloidogenic properties (49) . Interestingly, several reports have evidenced the presence of deposits containing elastin fragments, called elastotic material, in photodamaged skin, in atheromatous plaques, and in lung alveolae of patients with acute interstitial lung disease (49) . Although the nature of these deposits has not yet been fully characterized, the elastotic material was shown to contain amyloid-like fibers.…”