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Published ahead of print on August 14, 2003, doi:10.1165/rcmb.2002-0311OC

Am. J. Respir. Cell Mol. Biol., Volume 30, Number 3, March 2004, 367-378

A more recent version of this article appeared on March 1, 2004
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Submitted on December 20, 2002
Revised on August 14, 2003

Regulation of bone marrow and airway CD34+ eosinophils by IL-5

Brigita Sitkauskiene1, Anna-Karin Johansson2, Svetlana Sergejeva2, Samuel Lundin3, Margareta Sjostrand2, and Jan Lotvall2*

1 Respiratory Medicine and Allergology, Goteborg University, The Lung Pharmacology Group, Gothenburg, Sweden; Kaunas University of Medicine, Department of Pulmonology and Immunology, Kaunas, Lithuania, 2 Respiratory Medicine and Allergology, Goteborg University, The Lung Pharmacology Group, Gothenburg, Sweden, 3 Goteborg University, Department of Microbiology/Immunology, Gothenburg, Sweden

* To whom correspondence should be addressed. E-mail: jan.lotvall{at}mednet.gu.se.

The aim of this study was to evaluate the effect of a neutralizing anti-IL-5 monoclonal antibody (TRFK-5) on bone marrow and airway CD34+ and immature eosinophils. A focus was to determine to effect of the timing of treatment. Balb/c mice were OVA-sensitised and subsequently exposed to OVA from five to ten days via airway route. Animals were treated intraperitoneally with TRFK-5 or its isotype control (50µg) once at different time-points. Newly produced eosinophils were labelled using 5-bromo-2'-deoxyuridine (BrdU). BrdU+ and CD34+ eosinophil numbers were examined by immunocytochemistry. TRFK-5 reduced bone marrow immature eosinophils within three days. This effect was closely related to a reduction BrdU+ and CD34+ bone marrow eosinophils, and reduced numbers of blood eosinophils. However, BAL eosinophilia was not attenuated to the same degree. The effect of TRFK-5 was most prominent in the extended allergen-exposure protocol, where the treatment given in the middle of the exposure, with strongly reduced bone marrow CD34+ and immature bone marrow eosinophils, blood eosinophils as well as BAL BrdU+ eosinophils and BAL CD34+ eosinophils. These data argue that anti-IL-5 down-regulates eosinophilopoiesis within three days by action in the bone marrow, by inhibition of the early stages of eosinophil maturation from CD34+ cells.






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Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
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