Eotaxin expression in Sephadex-induced lung injury in rats.
The CC chemokine eotaxin is a potent and specific eosinophil chemoattractant. Eosinophil-dependent tissue injury has been shown to contribute to airway inflammation such as that in asthma. In the present study, We investigated eotaxin expression in a rat model of pulmonary inflammation (featuring accumulation of eosinophils) induced by intratracheal instillation of cross-linked dextran beads (Sephadex G200). Intratracheal instillation of 5 mg/kg Sephadex caused a time-dependent eosinophil infiltration into the lung, reaching a peak at 24 hours. Eotaxin mRNA in the lung paralleled the eosinophil influx. Eotaxin protein in bronchoalveolar (BAL) fluids and lung homogenates was shown by Western blot and immunostaining to be maximally expressed by 24 hours. Sephadex-induced lung injury, as measured by (125)I-labeled albumin leakage from the pulmonary vasculature, developed in a time-dependent manner. Intravenous injection of blocking antibody to eotaxin significantly decreased eosinophil infiltration and lung permeability. These data suggest that, in the Sephadex model of lung inflammation, eotaxin up-regulation mediates intrapulmonary accumulation of eosinophils and the development of lung injury.
Guo
R F
RF
Genomic Pathology Laboratory, Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602, USA.
Ward
P A
PA
Jordan
J A
JA
Huber-Lang
M
M
Warner
R L
RL
Shi
M M
MM
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003911:Dextrans; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007249:Inflammation; D007958:Leukocyte Count; D008171:Lung Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020318:Rats, Long-Evans
C515458:Ccl11 protein, rat; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D003911:Dextrans; D012333:RNA, Messenger; C025614:sephadex