title: Neutrophil structural changes associated with chronic endotoxemia and lung injury.
abstract: Previous studies showed that chronic endotoxemia induces thickening of the alveolar wall of rabbits. The present study examines cellular changes associated with this process and attempts to define the role of PMN in this response. Rabbits received i.v. injections of either Escherichia coli lipopolysaccharide (LPS) or saline (control), 2-3 times weekly, for 28 weeks. Peripheral blood mature and immature polymorphonuclear leukocyte (PMN) cell counts were determined on Wright-stained blood smears. Lung histological analysis was performed by both light and electron microscopy. FITC-Maclura pomifera was used to identify type II cells and diaminobenzidine tetrahydrochloride-H2O2 was employed to localize peroxidase. The results show that the LPS-induced neutrophilia is associated with an increase in the circulating band cells which is consistent with active bone marrow release. PMN in the pulmonary microvessels display structural features characteristic of phagocytosis and active macromolecule synthesis. Endothelial cells, adjacent to these PMN, show numerous coated pits and large inclusions suggestive of endocytosis. The LPS-induced thickening of the alveolar wall is associated with leukocyte migration into the interstitial and alveolar spaces. Some interstitial PMN are fragmented and surrounded by dispersed elements of the connective tissue, while others appear activated and are closely associated with hyperactive fibroblasts and alveolar type II cells. The number of alveolar type II cells has increased twofold. These results show that chronic endotoxemia in rabbits causes structural changes in PMN, endothelium, interstitium, and epithelium. PMN structural changes are consistent with enhanced functional properties and their close association with modified regions of the lung parenchyma suggest that PMN play an important role in the process of this lung injury and repair.
authors.affiliation: University of British Columbia, Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada. Mklut@prl.pulmonary.ubc.ca
authors.forename: M E
authors.initials: ME
authors.lastname: Klut
authors.forename: S F
authors.initials: SF
authors.lastname: van Eeden
authors.forename: J C
authors.initials: JC
authors.lastname: Hogg
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000473:pathology; D019446:Endotoxemia / Q000473:pathology*; D004848:Epithelium / Q000473:pathology; D004926:Escherichia coli; D005260:Female; D005347:Fibroblasts / Q000648:ultrastructure; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000098:blood supply / Q000473:pathology*; D008833:Microcirculation / Q000473:pathology; D008854:Microscopy, Electron; D009504:Neutrophils / Q000648:ultrastructure*; D010587:Phagocytosis; D011650:Pulmonary Alveoli / Q000473:pathology; D011817:Rabbits
chemical_list: D008070:Lipopolysaccharides