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Eosinophil recruitment in type-2 hypersensitivity pulmonary granulomas: source and contribution of monocyte chemotactic protein-3 (CCL7).

AbstractMonocyte 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.
AuthorsXiao-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.)
JournalThe American journal of pathology (Am J Pathol) Vol. 161 Issue 1 Pg. 257-66 (Jul 2002) ISSN: 0002-9440 United States
PMID12107110 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antibodies
  • Antigens, Helminth
  • Ccl7 protein, mouse
  • Chemokine CCL7
  • Cytokines
  • Monocyte Chemoattractant Proteins
  • Interleukin-4
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)