Local proliferation and mobilization of CCR3(+)  CD34(+) eosinophil-lineage-committed cells in the lung.
Emerging evidence suggests that haematopoietic CD34(+) progenitor cells migrate from bone marrow (BM) to sites of allergen exposure where they can undergo further proliferation and final maturation, potentially augmenting the degree of tissue inflammation. In the current study we used a well-characterized mouse model of allergen-induced airway inflammation to determine the role of CCR3 receptor-ligand interactions in the migration and function of CD34(+) cells. Allergen exposure significantly increased BM, blood and airway CD34(+) CCR3(+) cells as well as airway CD34(+) CCR3(+) stem cell antigen-1-positive (Sca-1(+) ) and CD34(+) CD45(+) interleukin-5 receptor-α-positive (IL-5Rα(+) ) cells. A portion of the newly produced CD34(+) CCR3(+), Sca-1(+) CCR3(+) and IL-5Ralpha(+) lung cells showed a significant proliferative capacity in response to allergen when compared with saline-treated animals. In addition, in vitro colony formation of lung CD34(+) cells was increased by IL-5 or eotaxin-2 whereas eotaxin-2 had no effect on BM CD34(+) cells. Furthermore, both eotaxin-1 and eotaxin-2 induced migration of BM and blood CD34(+) CCR3(+) cells in vitro. These data suggest that the CCR3/eotaxin pathway is involved in the regulation of allergen-driven in situ haematopoiesis and the accumulation/mobilization of eosinophil-lineage-committed progenitor cells in the lung. Hence, targeting both IL-5 and CCR3-mediated signalling pathways may be required to control the inflammation associated with allergen-induced asthma.
Rådinger
Madeleine
M
Krefting Research Centre, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. madeleine.radinger@gu.se
Bossios
Apostolos
A
Sjöstrand
Margareta
M
Lu
You
Y
Malmhäll
Carina
C
Dahlborn
Anna-Karin
AK
Lee
James J
JJ
Lötvall
Jan
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D049109:Cell Proliferation; D004804:Eosinophils / Q000166:cytology* / Q000276:immunology; D053666:Interleukin-5 Receptor alpha Subunit / Q000276:immunology; D008168:Lung / Q000166:cytology* / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage; D054397:Receptors, CCR3 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; C515351:Ccr3 protein, mouse; D053666:Interleukin-5 Receptor alpha Subunit; D054397:Receptors, CCR3; C527275:interleukin-5- receptor alpha, mouse; D010047:Ovalbumin