Eotaxin and eotaxin receptor (CCR3) expression in Sephadex particle-induced rat lung inflammation.
The beta chemokine eotaxin is a potent eosinophil activator and chemoattractant. We examined immunohistochemically eotaxin protein expression in a range of normal rat tissues and in rat lung during Sephadex particle-induced pulmonary inflammation. The time course of eotaxin expression in lung at various time points after Sephadex administration was related to the appearance of eosinophils in the bronchoalveolar lavage fluid and tissue distribution of eotaxin receptor (CCR3) positive cells. Results showed that eotaxin protein was constitutively expressed by both lung airway epithelial cells and gut epithelial cells in normal tissues in the absence of inflammation. During Sephadex induced pulmonary inflammation, eotaxin expression increased in alveolar macrophages prior to the major increase in eosinophil numbers which reached a peak at 72 h. The pattern of eotaxin pulmonary expression and the location of CCR3 receptor positive cells suggest a chemoattractant gradient resulting in migration firstly into the tissue and subsequently through the airway epithelium into the airways. Treatment of rats with the glucocorticoid dexamethasone or the immunosuppressant cyclosporin A reduced eosinophil entry into lung tissue and airways but had no apparent effect on eotaxin expression in vivo, indicating that both these drugs inhibit eosinophil recruitment either by an eotaxin-independent mechanism, or by targetting factors that synergise with eotaxin, or an event post eotaxin expression.
Harrington
P M
PM
Department of Immunology, University of Liverpool, Alderley Park, Macclesfield, UK.
Newton
D J
DJ
Williams
C M
CM
Hunt
J A
JA
Dearman
R J
RJ
Kimber
I
I
Coleman
J W
JW
Flanagan
B F
BF
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002634:Chemotaxis, Leukocyte; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D003911:Dextrans; D004804:Eosinophils / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005782:Gels; D005938:Glucocorticoids / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008168:Lung / Q000187:drug effects; D008297:Male; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000378:metabolism*
C515458:Ccl11 protein, rat; C515352:Ccr3 protein, rat; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D003911:Dextrans; D005782:Gels; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D003907:Dexamethasone; D016572:Cyclosporine; C025614:sephadex