| Abstract | Monocyte chemotactic protein-3 (MCP-3/CCL7) has potent eosinophil chemoattractant properties. The present study determined its relative contribution to the formation of Th2 cytokine-mediated (type-2) eosinophil-rich interstitial lung granulomas induced by antigens of Schistosoma mansoni eggs. Both MCP-3 transcripts and protein levels were more strongly expressed in lungs with type-2 than with type-1 (mycobacterial antigen-elicited Th1-mediated) granulomas. In vivo treatment with neutralizing antibodies demonstrated that MCP-3 abrogated eosinophil accumulation in type-2 lesions by 40 to 50%. Immunohistochemical staining revealed that MCP-3 localized to vessels in or near granulomas suggesting that endothelial cells were an important in situ source of MCP-3. Maximal MCP-3 transcript expression was abrogated by anti-interleukin-4 treatment. Furthermore, cultured mouse lung endothelial cells displayed augmented MCP-3 production in response to interleukin-4. Together, these results suggest that MCP-3 contributes to a significant component of eosinophil recruitment in the type-2 interstitial granuloma formation and Th2 cytokines promote its production. |
| Authors | Xiao-Zhou Shang, Bo-Chin Chiu, Valerie Stolberg, Nicholas W Lukacs, Steven L Kunkel, Hedwig S Murphy, Stephen W Chensue
(Affiliation: Department of Pathology, University of Michigan Hospitals, Ann Arbor, USA.)
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| Journal | The American journal of pathology
(Am J Pathol)
Vol. 161
Issue 1
Pg. 257-66
(Jul 2002)
ISSN: 0002-9440 United States |
| PMID | 12107110
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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| Chemical References |
- Antibodies
- Antigens, Helminth
- Ccl7 protein, mouse
- Chemokine CCL7
- Cytokines
- Monocyte Chemoattractant Proteins
- Interleukin-4
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| Topics |
- Animals
- Antibodies
(pharmacology)
- Antigens, Helminth
(immunology)
- Blood Vessels
(metabolism)
- Cell Movement
- Chemokine CCL7
- Cytokines
- Endothelium, Vascular
(metabolism)
- Eosinophils
(pathology, physiology)
- Female
- Granuloma, Respiratory Tract
(immunology, pathology, physiopathology)
- Hypersensitivity
(immunology)
- Interleukin-4
(immunology)
- Lung
(metabolism)
- Lung Diseases
(immunology, pathology, physiopathology)
- Mice
- Mice, Inbred CBA
- Monocyte Chemoattractant Proteins
(antagonists & inhibitors, metabolism)
- Pulmonary Circulation
- Schistosoma mansoni
(immunology)
- Th2 Cells
(immunology)
|