Monocyte chemoattractant protein (MCP)-4 expression in the airways of patients with asthma. Induction in epithelial cells and mononuclear cells by proinflammatory cytokines.
Chemokines are chemotactic cytokines that play an important role in recruiting leukocytes in allergic inflammation. Monocyte chemoacctractant protein (MCP)-4 is a CC chemokine with potent chemotactic activities for eosinophils, monocytes, T lymphocytes, and basophils and therefore represents a good candidate to participate in allergic reactions. To determine if MCP-4 plays a role in asthma, we have investigated the expression of MCP-4 messenger RNA (mRNA) and protein in the airways of patients with asthma and normal control subjects by in situ hybridization and immunohistochemistry. We found that MCP-4 mRNA and protein was significantly upregulated in the epithelium and submucosa of bronchial biopsies and in the bronchoalveolar lavage (BAL) cells of patients with asthma compared with normal control subjects (p < 0. 01). In addition, MCP-4 protein was significantly elevated in the BAL fluid of patients with atopic asthma when compared with normal control subjects (p < 0.01) and there was a significant correlation between MCP-4, eotaxin, and eosinophils. In support of our in situ findings demonstrating MCP-4 expression in epithelial cells and mononuclear cells in vivo, we have found that MCP-4 expression can be induced in these cells in vitro by tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). Interferon-gamma (IFN-gamma) acted synergistically with TNF-alpha and IL-1beta in the induction of mRNA MCP-4 mRNA expression in A549 cells, whereas the glucocorticoid dexamethasone diminished the cytokine-induced expression of MCP-4. Our findings demonstrate that MCP-4 is upregulated in the airways of patients with asthma and suggest that MCP-4 plays a role in the recruitment of eosinophils into the airways of patients with asthma.
Meakins-Christie Laboratories and Departments of Medicine and Pathology, McGill University, Montreal, Quebec, Canada.
B
B
Lamkhioued
E A
EA
Garcia-Zepeda
S
S
Abi-Younes
H
H
Nakamura
S
S
Jedrzkiewicz
L
L
Wagner
P M
PM
Renzi
Z
Z
Allakhverdi
C
C
Lilly
Q
Q
Hamid
A D
AD
Luster
D000906:Antibodies; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000166:cytology; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D000906:Antibodies; C515456:CCL11 protein, human; C099677:CCL13 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D007375:Interleukin-1; D018945:Monocyte Chemoattractant Proteins; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma; D003513:Cycloheximide