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PMID: 15466387 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Role of CCR4 ligands, CCL17 and CCL22, during Schistosoma mansoni egg-induced pulmonary granuloma formation in mice.

The American journal of pathology ·Vol. 165 ·No. 4 ·2004-10-00 ·Pages 1211-21

Jakubzick C, Wen H, Matsukawa A, Keller M, Kunkel SL, Hogaboam CM

Abstract

Controversy persists pertaining to the role of CCR4 ligands, namely CCL17 (or thymus and activation regulated chemokine; TARC) and CCL22 (or macrophage-derived chemokine; MDC), in Th2-type cytokine-dominated responses in the lung. Accordingly, the present study addressed the relative role of each of these CC chemokines during an evolving pulmonary granulomatous response elicited by the intrapulmonary embolization of live Schistosoma mansoni eggs into S. mansoni-sensitized mice. CCL22 protein expression peaked at day 4, but CCL17 levels were not increased significantly at any time after egg challenge. CCR4 transcript and protein expression were highest at day 8 after egg embolization and CCR4 protein was prominently expressed in macrophages surrounding S. mansoni eggs. Systemic immunoneutralization of CCL22 from the time of egg injection into S. mansoni-sensitized mice for 8 days significantly decreased CCR4 protein expression, the eosinophil content, the overall size of the egg granuloma, and its hydroxyproline content. Whole lung levels of interferon-gamma were also significantly increased at day 8 in anti-CCL22-treated mice. The systemic immunoneutralization of CCL17 had a lesser effect on all of the granuloma parameters listed above, but this antibody treatment significantly decreased granuloma hydroxyproline content to a greater extent than the anti-CCL22 antibody treatment. In addition, the immunoneutralization of CCL17 significantly increased whole lung levels of interleukin (IL)-4, IL-5, IL-13, transforming growth factor-beta, IL-12, and tumor necrosis factor-alpha at day 8 after egg infusion. Thus, these studies demonstrate a major role for CCL22 and a lesser role for CCL17 during an evolving S. mansoni egg granuloma in the lung.

MeSH Terms
Animals Chemokine CCL17 Chemokine CCL22 Chemokines, CC/immunology Disease Models, Animal Enzyme-Linked Immunosorbent Assay Granuloma, Respiratory Tract/etiology,immunology Immunohistochemistry Interferon-gamma/immunology Interleukins/immunology Lung/immunology,pathology Mice Ovum/immunology Receptors, CCR4 Receptors, Chemokine/immunology Reverse Transcriptase Polymerase Chain Reaction Schistosoma mansoni/immunology Schistosomiasis mansoni/immunology Transforming Growth Factor beta/immunology Tumor Necrosis Factor-alpha/immunology
Chemicals
Ccl17 protein, mouse Ccl22 protein, mouse Ccr4 protein, mouse Chemokine CCL17 Chemokine CCL22 Chemokines, CC Interleukins Receptors, CCR4 Receptors, Chemokine Transforming Growth Factor beta Tumor Necrosis Factor-alpha Interferon-gamma
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Jakubzick Claudia
Department of Pathology, University of Michigan Medical School, 1301 Catherine Rd., Ann Arbor, MI 48109-0602, USA.
Wen Haitao
Matsukawa Akihiro
Keller Maya
Kunkel Steven L
Hogaboam Cory M
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)63381-0
Published
2004-10-00
Pages
1211-21
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1618636
Subset
IM
Grants
NIAID NIH HHS · T32 AI007413 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)63381-0 PMC Full Text View journal details
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