title: TRALI is due to pulmonary venule damage from leucocytes with cholesterol crystal formation.
abstract: BACKGROUND
  There are two presumed mechanisms for the pulmonary oedema in transfusion-related acute lung injury (TRALI). One is antibodies to leucocytes while the other is biologically active lipids. We evaluated the vascular injury due to the former.
  
  
  METHODS
  The pulmonary vasculature was studied by light microscopy (LM) and scanning electron microscopy (SEM) in three fatal cases of TRALI and compared with that of two autopsied control patients. Lung tissue from two of the TRALI cases and both controls was studied by gas chromatography-mass spectroscopy (GC-MS) to identify crystals present in the former.
  
  
  RESULTS
  All three TRALI cases exhibited massive pulmonary oedema by weight and light microscopy and extensive defects by SEM in the endothelium of venules of the lungs. Such endothelial defects were absent in controls. Thrombi, composed of crystals, were present in venules and small veins diffusely throughout the lungs in Case 1. Similar crystals were identified in Case 2. The crystals in the lung vessels were identified morphologically as cholesterol and were proximate to the cytoplasmic defects of the endothelial surfaces. By GC-MS, there were markedly elevated levels of cholesterol and fatty acids in the two TRALI lungs tested compared with the lungs of the two controls.
  
  
  CONCLUSIONS
  Pulmonary damage in TRALI is related to formation of cholesterol crystals that appear to pierce endothelial membranes of venules. The endothelial defects lead to plasma extravasation into the alveoli causing TRALI.
authors.affiliation: Department of Pathology and Laboratory Medicine, Davis Medical Center, University of California, Sacramento, CA, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Jensen
authors.forename: J M
authors.initials: JM
authors.lastname: Galante
authors.forename: P E
authors.initials: PE
authors.lastname: Kysar
authors.forename: V V
authors.initials: VV
authors.lastname: Tolstikov
authors.forename: K J
authors.initials: KJ
authors.lastname: Reddy
authors.forename: P V
authors.initials: PV
authors.lastname: Holland
mesh_terms: D055371:Acute Lung Injury / Q000097:blood* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D000328:Adult; D002784:Cholesterol / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology; D011654:Pulmonary Edema / Q000097:blood* / Q000276:immunology; D065227:Transfusion Reaction; D055815:Young Adult
chemical_list: D002784:Cholesterol