Pathogenesis of murine experimental allergic rhinitis: a study of local and systemic consequences of IL-5 deficiency.

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.

• 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)

Chemical References

• Antigens, CD34
• Interleukin-5
• Receptors, Interleukin
• Receptors, Interleukin-5
• Histamine
• Methylcellulose
• Ovalbumin
• Leukocyte Common Antigens

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)