Abstract |
Recent studies have demonstrated an important role for IL-5-dependent bone marrow eosinophil progenitors in allergic inflammation. However, studies using anti-IL-5 mAbs in human asthmatics have failed to suppress lower airway hyperresponsiveness despite suppression of eosinophilia; therefore, it is critical to examine the role of IL-5 and bone marrow responses in the pathogenesis of allergic airway disease. To do this, we studied the effects of IL-5 deficiency (IL-5(-/-)) on bone marrow function as well as clinical and local events, using an established experimental murine model of allergic rhinitis. Age-matched IL-5(+/+) and IL-5(-/-) BALB/c mice were sensitized to OVA followed by 2 wk of daily OVA intranasal challenge. IL-5(-/-) OVA-sensitized mice had significantly higher nasal mucosal CD4(+) cells and basophilic cell counts as well as nasal symptoms and histamine hyperresponsiveness than the nonsensitized group; however, there was no eosinophilia in either nasal mucosa or bone marrow; significantly lower numbers of eosinophil/basophil CFU and maturing CFU eosinophils in the presence of recombinant mouse IL-5 in vitro; and significantly lower expression of IL-5Ralpha on bone marrow CD34(+)CD45(+) progenitor cells in IL-5(-/-) mice. These findings suggest that IL-5 is required for normal bone marrow eosinophilopoiesis, in response to specific Ag sensitization, during the development of experimental allergic rhinitis. However, the results also suggest that suppression of the IL-5-eosinophil pathway in this model of allergic rhinitis may not completely suppress clinical symptoms or nasal histamine hyperresponsiveness, because of the existence of other cytokine-progenitor pathways that may induce and maintain the presence of other inflammatory cell populations.
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Authors | Hiroko Saito, Koichiro Matsumoto, Avram E Denburg, Lynn Crawford, Russ Ellis, Mark D Inman, Roma Sehmi, Kiyoshi Takatsu, Klaus I Matthaei, Judah A Denburg |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 168
Issue 6
Pg. 3017-23
(Mar 15 2002)
ISSN: 0022-1767 [Print] United States |
PMID | 11884474
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, CD34
- Interleukin-5
- Receptors, Interleukin
- Receptors, Interleukin-5
- Histamine
- Methylcellulose
- Ovalbumin
- Leukocyte Common Antigens
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Topics |
- Animals
- Antigens, CD34
(biosynthesis)
- Basophils
(pathology)
- Bone Marrow
(metabolism, pathology)
- Cell Differentiation
(drug effects, genetics, immunology)
- Cells, Cultured
- Colony-Forming Units Assay
- Eosinophils
(drug effects, pathology)
- Female
- Hematopoietic Stem Cells
(immunology, metabolism)
- Histamine
(administration & dosage)
- Interleukin-5
(deficiency, genetics, metabolism, physiology)
- Leukocyte Common Antigens
(biosynthesis)
- Male
- Methylcellulose
(pharmacology)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Nasal Mucosa
(pathology)
- Ovalbumin
(administration & dosage, immunology)
- Receptors, Interleukin
(biosynthesis)
- Receptors, Interleukin-5
- Rhinitis, Allergic, Perennial
(diagnosis, genetics, immunology, pathology)
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