Eosinophil recruitment in type-2 hypersensitivity pulmonary granulomas: source and contribution of monocyte chemotactic protein-3 (CCL7).
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.
Shang
Xiao-Zhou
XZ
Department of Pathology, University of Michigan Hospitals, Ann Arbor, USA.
Chiu
Bo-Chin
BC
Stolberg
Valerie
V
Lukacs
Nicholas W
NW
Kunkel
Steven L
SL
Murphy
Hedwig S
HS
Chensue
Stephen W
SW
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000947:Antigens, Helminth / Q000276:immunology*; D001808:Blood Vessels / Q000378:metabolism; D002465:Cell Movement; D054410:Chemokine CCL7; D016207:Cytokines; D004730:Endothelium, Vascular / Q000378:metabolism; D004804:Eosinophils / Q000473:pathology / Q000502:physiology*; D005260:Female; D015769:Granuloma, Respiratory Tract / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006967:Hypersensitivity / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008808:Mice, Inbred CBA; D018945:Monocyte Chemoattractant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011652:Pulmonary Circulation; D012550:Schistosoma mansoni / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000906:Antibodies; D000947:Antigens, Helminth; C515451:Ccl7 protein, mouse; D054410:Chemokine CCL7; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; D015847:Interleukin-4