Glucocorticosteroids inhibit mRNA expression for eotaxin, eotaxin-2, and monocyte-chemotactic protein-4 in human airway inflammation with eosinophilia.
How eosinophils are preferentially recruited to inflammatory sites remains elusive, but increasing evidence suggests that chemokines that bind to the CCR3 participate in this process. In this study, we investigated the transcript levels and chemotactic activity of CCR3-binding chemokines in nasal polyps, a disorder often showing prominent eosinophilia. We found that mRNA expression for eotaxin, eotaxin-2, and monocyte-chemotactic protein-4 was significantly increased in nasal polyps compared with turbinate mucosa from the same patients, or histologically normal nasal mucosa from control subjects. Interestingly, the novel CCR3-specific chemokine, eotaxin-2, showed the highest transcript levels. Consistent with these mRNA data, polyp tissue fluid exhibited strong chemotactic activity for eosinophils that was significantly inhibited by a blocking Ab against CCR3. When patients were treated systemically with glucocorticosteroids, the mRNA levels in the polyps were reduced to that found in turbinate mucosa for all chemokines. Together, these findings suggested an important role for CCR3-binding chemokines in eosinophil recruitment to nasal polyps. Such chemokines, therefore, most likely contribute significantly in the pathogenesis of eosinophil-related disorders; and the reduced chemokine expression observed after steroid treatment might reflect, at least in part, how steroids inhibit tissue accumulation of eosinophils.
Laboratory for Immunohistochemistry, Institute of Pathology, Department of Ear, Nose, and Throat, University of Oslo, The National Hospital, Rikshospitalet, Norway. f.l.jahnsen@labmed.uio.no
F L
FL
Jahnsen
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R
Haye
E
E
Gran
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P
Brandtzaeg
F E
FE
Johansen
D000328:Adult; D000368:Aged; D001826:Body Fluids / Q000276:immunology; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D002631:Chemotactic Factors, Eosinophil / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D004802:Eosinophilia / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D018945:Monocyte Chemoattractant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D009298:Nasal Polyps / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D011241:Prednisone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014420:Turbinates / Q000473:pathology
C515456:CCL11 protein, human; C099677:CCL13 protein, human; C515484:CCL24 protein, human; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D011241:Prednisone