Eosinophil chemotactic chemokines (eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4), and C-C chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (Intrinsic) asthmatics.
Atopic (AA) and nonatopic (NAA) asthma are characterized by chronic inflammation and local tissue eosinophilia. Many C-C chemokines are potent eosinophil chemoattractants and act predominantly via the CCR3. We examined the expression of eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), MCP-4, and CCR3 in the bronchial mucosa from atopic (AA) and nonatopic (intrinsic; NAA) asthmatics and compared our findings with atopic (AC) and nonatopic nonasthmatic controls (NC). Cryostat sections were processed for immunohistochemistry (IHC), in situ hybridization (ISH), and double IHC/ISH. Compared with AC and NC, the numbers of EG2+ cells and the cells expressing mRNA for eotaxin, eotaxin-2, RANTES, MCP-3, MCP-4, and CCR3 were significantly increased in AA and NAA (p < 0.01). Nonsignificant differences in these variants were observed between AA and NAA and between AC and NC. Significant correlations between the cells expressing eotaxin or CCR3 and EG2+ eosinophils in the bronchial tissue were also observed for both AA (p < 0.01) and NAA (p = 0.01). Moreover, in the total asthmatic group (AA + NAA) there was a significant inverse correlation between the expression of eotaxin and that of the histamine PC20 (p < 0.05). Sequential IHC/ISH showed that cytokeratin+ epithelial cells, CD31+ endothelial cells, and CD68+ macrophages were the major sources of eotaxin, eotaxin-2, RANTES, MCP-3, and MCP-4. There was no significantly different distribution of cells expressing mRNA for these chemokines between atopic and nonatopic asthma. These findings suggest that multiple C-C chemokines, acting at least in part via CCR3, contribute to bronchial eosinophilia in both atopic and nonatopic asthma.
Ying
S
S
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom.
Meng
Q
Q
Zeibecoglou
K
K
Robinson
D S
DS
Macfarlane
A
A
Humbert
M
M
Kay
A B
AB
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000145:classification / Q000276:immunology*; D001706:Biopsy; D001980:Bronchi / Q000276:immunology* / Q000601:surgery; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D002631:Chemotactic Factors, Eosinophil / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000145:classification / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D020545:Respiratory Mucosa / Q000276:immunology
C515350:CCR3 protein, human; D018925:Chemokines; D002631:Chemotactic Factors, Eosinophil; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine