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PMID: 9739047 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Circulating, but not local lung, IL-5 is required for the development of antigen-induced airways eosinophilia.

The Journal of clinical investigation ·Vol. 102 ·No. 6 ·1998-09-15 ·Pages 1132-41

Wang J, Palmer K, Lŏtvall J, Milan S, Lei XF, Matthaei KI, Gauldie J, Inman MD, Jordana M, Xing Z

Abstract

IL-5 is induced locally in the lung and systemically in the circulation during allergic airways eosinophilic inflammation both in humans and experimental animals. However, the precise role of local and systemic IL-5 in the development of allergic airways eosinophilia remains to be elucidated. In our current study, we demonstrate that compared with their IL-5(+/+) counterparts, IL-5(-/-) mice lacked an IL-5 response both in the lung and peripheral blood, yet they released similar amounts of IL-4, eotaxin, and MIP-1alpha in the lung after ovalbumin (OVA) sensitization and challenge. At cellular levels, these mice failed to develop peripheral blood and airways eosinophilia while the responses of lymphocytes, neutrophils, and macrophages remained similar to those in IL-5(+/+) mice. To dissect the relative role of local and systemic IL-5 in this model, we constructed a gene transfer vector expressing murine IL-5. Intramuscular IL-5 gene transfer to OVA-sensitized IL-5(-/-) mice led to raised levels of IL-5 compartmentalized to the circulation and completely reconstituted airways eosinophilia upon OVA challenge, which was associated with reconstitution of eosinophilia in the bone marrow and peripheral blood. Significant airways eosinophilia was observed for at least 7 d in these mice. In contrast, intranasal IL-5 gene transfer, when rendered to give rise to a significant but compartmentalized level of transgene protein IL-5 in the lung, was unable to reconstitute airways eosinophilia in OVA-sensitized IL-5(-/-) mice upon OVA-challenge, which was associated with a lack of eosinophilic responses in bone marrow and peripheral blood. Our findings thus provide unequivocal evidence that circulating but not local lung IL-5 is critically required for the development of allergic airways eosinophilia. These findings also provide the rationale for developing strategies to target circulating IL-5 and/or its receptors in bone marrow to effectively control asthmatic airways eosinophilia.

MeSH Terms
Adenoviridae/genetics Animals Asthma/etiology,immunology,pathology Blood/immunology Bone Marrow/immunology Chemokine CCL11 Chemokine CCL3 Chemokine CCL4 Chemokines, CC Cytokines/analysis Eosinophilia Gene Transfer Techniques Genetic Vectors Interleukin-5/blood,deficiency,genetics Lung/immunology,pathology Macrophage Inflammatory Proteins/analysis Male Mice Mice, Inbred C57BL Mice, Knockout Ovalbumin/immunology Pulmonary Eosinophilia/etiology,immunology,pathology
Chemicals
Ccl11 protein, mouse Chemokine CCL11 Chemokine CCL3 Chemokine CCL4 Chemokines, CC Cytokines Interleukin-5 Macrophage Inflammatory Proteins Ovalbumin
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Wang J
Immunology and Infection Program, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Palmer K
Lŏtvall J
Milan S
Lei X F
Matthaei K I
Gauldie J
Inman M D
Jordana M
Xing Z
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI2686
Published
1998-09-15
Pages
1132-41
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC509096
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI2686 PMC Full Text View journal details
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