Regulation of bone marrow and airway CD34+ eosinophils by interleukin-5.
The aim of this study was to evaluate the effect of a neutralizing anti-interleukin (IL)-5 monoclonal antibody (TRFK-5) on bone marrow and airway CD34(+) and immature eosinophils. A focus was to determine the effect of the timing of treatment. Balb/c mice were ovalbumin-sensitized and subsequently exposed to ovalbumin for 5-10 d via airway route. Animals were treated intraperitoneally with TRFK-5 or its isotype control (50 microg) once at different time points. Newly produced eosinophils were labeled using 5-bromo-2'-deoxyuridine (BrdU). BrdU(+) and CD34(+) eosinophil numbers were examined by immunocytochemistry. TRFK-5 reduced bone marrow immature eosinophils within 3 d. This effect was closely related to a reduction of BrdU(+) and CD34(+) bone marrow eosinophils, and reduced numbers of blood eosinophils. However, bronchoalveolar lavage (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 was 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 downregulates eosinophilopoiesis within 3 d by action in the bone marrow, by inhibition of the early stages of eosinophil maturation from CD34(+) cells.
Sitkauskiene
Brigita
B
The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Internal Medicine, Göteborg University, Guldhedsgatan 10A, 413 46 Gothenburg, Sweden.
Johansson
Anna-Karin
AK
Sergejeva
Svetlana
S
Lundin
Samuel
S
Sjöstrand
Margareta
M
Lötvall
Jan
J
D000485:Allergens / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018952:Antigens, CD34 / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D002455:Cell Division / Q000187:drug effects; D004802:Eosinophilia / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D015848:Interleukin-5 / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
D000485:Allergens; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D015848:Interleukin-5; D010047:Ovalbumin; D001973:Bromodeoxyuridine