The kinetics of allergen-induced eotaxin level in nasal lavage fluid: its key role in eosinophil recruitment in nasal mucosa.
Eotaxin (CCL11) is a potent eosinophil chemoattractant belonging to the C-C chemokine. To evaluate the role of eotaxin in eosinophilic inflammation in nasal mucosa, we investigated the levels of eosinophil chemoattractants in nasal lavage fluids obtained after antigen challenge, compared with eosinophil counts and eosinophil protein X (EPX) levels. In subjects with allergic rhinitis, allergen challenge led to parallel increases in eosinophil counts, levels of EPX, and eotaxin concentrations in nasal lavage fluid. The levels of eotaxin in lavage samples showed strong correlation with lavage levels of eosinophil counts and EPX. Normal subjects had few, if any, eosinophils and EPX as well as the measured parameters in their nasal lavage fluids before and after antigen challenge. In our experiments of eosinophil endothelial transmigration (TEM) assay using the nasal microvascular endothelial cells, eotaxin showed the most potent effect among various eosinophil chemoattractants. In addition, treatment of eosinophils with anti-CCR-3 mAb significantly blocked eosinophil TEM induced by homogenate of nasal mucosa. These results indicate that eotaxin has an important role in eosinophil-dependent inflammation in nasal mucosa and suggest that blocking eotaxin or CCR-3 might be useful for new therapeutic tools of allergic rhinitis.
Terada
N
N
Department of Otorhinolaryngology, Chiba University School of Medicine, Chiba, Japan. terada@med.m.chiba-u.ac.jp
Hamano
N
N
Kim
W J
WJ
Hirai
K
K
Nakajima
T
T
Yamada
H
H
Kawasaki
H
H
Yamashita
T
T
Kishi
H
H
Nomura
T
T
Numata
T
T
Yoshie
O
O
Konno
A
A
D000485:Allergens / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D016022:Case-Control Studies; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000032:analysis / Q000276:immunology; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000032:analysis / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007249:Inflammation; D007958:Leukocyte Count; D017817:Nasal Lavage Fluid / Q000737:chemistry* / Q000276:immunology*; D009297:Nasal Mucosa / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009299:Nasal Provocation Tests; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
D000485:Allergens; D000911:Antibodies, Monoclonal; C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D054397:Receptors, CCR3; D019707:Receptors, Chemokine