Pulmonary eosinophilia and granulomatous pulmonary arteritis induced in rats by intravenous Sephadex.
Airway eosinophilia has been proposed as a major pathogenetic event in bronchial asthma and airway hyperresponsiveness. Intravenous injection of Sephadex G200 in rats induces pulmonary and blood eosinophilia and alters pulmonary responsiveness to 5-hydroxytryptamine. To characterize the early pulmonary inflammatory responses following Sephadex administration, and to determine the timing of the onset of pulmonary eosinophilia relative to blood eosinophilia, Sprague-Dawley rats were injected intravenously with Sephadex G200 beads. Lungs and other tissues were examined by light and transmission electron microscopy at 4, 12, 24, 48, 72, and 96 hours after injection. Blood eosinophil counts were determined at 0, 24, and 96 hours after injection. Sephadex beads were trapped initially in small caliber muscular pulmonary arteries associated with terminal bronchioles and in intra-acinar locations. There was marked infiltration of eosinophils and macrophages around the beads and into arterial walls and edematous periarterial and peribronchiolar connective tissue as early as 4 hours after injection. Periarterial-peribronchiolar eosinophil aggregates peaked in density at 24 and 48 hours. Macrophages and multinucleated cells dominated the inflammatory cell responses in arteries immediately surrounding partially degraded Sephadex beads from 24 to 96 hours. Bone marrow eosinophilopoiesis and blood eosinophilia were not detected until 96 hours. We conclude that Sephadex induces pulmonary eosinophilia prior to blood eosinophilia and suggest that Sephadex may induce pulmonary release of one or more eosinophil chemotactic substance(s). This model may prove useful in the study of factors that influence eosinophil migration into the lung in various disease states.
Sorden
S D
SD
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison.
Lemanske
R F
RF
Castleman
W L
WL
D000818:Animals; D001158:Arteries; D001167:Arteritis / Q000209:etiology* / Q000473:pathology; D003911:Dextrans / Q000008:administration & dosage; D004804:Eosinophils / Q000648:ultrastructure; D006099:Granuloma / Q000209:etiology; D007275:Injections, Intravenous; D008168:Lung / Q000098:blood supply* / Q000473:pathology / Q000648:ultrastructure; D008171:Lung Diseases / Q000209:etiology; D008264:Macrophages / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008863:Microspheres; D011657:Pulmonary Eosinophilia / Q000209:etiology* / Q000473:pathology; D051381:Rats
D003911:Dextrans; C025614:sephadex