FTY720 regulates bone marrow egress of eosinophils and modulates late-phase skin reaction in mice.
Eosinophilia in the blood and skin is frequently observed in patients with certain inflammatory skin diseases, such as atopic dermatitis. However, the mechanism underlying eosinophil circulation and the role of eosinophils in cutaneous immune responses remain unclear. In repeated hapten application-induced cutaneous responses in BALB/c mice, the administration of FTY720 before the last challenge decreased the number of skin-infiltrating eosinophils and reduced the late-phase reaction. A similar reduction of the late-phase reaction was observed by a sphingosine-1-phosphate G protein-coupled receptor (S1P1)-selective agonist, SEW2871. We monitored numerous alterations of eosinophils in the blood, spleen, bone marrow, and lymph nodes of interleukin-5 transgenic mice, used as an eosinophilia model, following FTY720 administration. The number of circulating eosinophils was significantly decreased after treatment with FTY720, and eosinophils accumulated in the bone marrow. In addition, eosinophils expressed S1P1, S1P3, and S1P4 mRNAs, and their chemotactic response to S1P was abolished by FTY720 as well as by SEW2871. These findings suggest that FTY720 affects the number of eosinophils in both the blood and skin by inhibiting the egress of eosinophils from the bone marrow and thus downmodulating the late-phase reaction.
Sugita
Kazunari
K
Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan. k-sugita@med.uoeh-u.ac.jp
Kabashima
Kenji
K
Sakabe
Jun-Ichi
J
Yoshiki
Ryutaro
R
Tanizaki
Hideaki
H
Tokura
Yoshiki
Y
D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D002465:Cell Movement; D002633:Chemotaxis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D000068876:Fingolimod Hydrochloride; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D015848:Interleukin-5 / Q000502:physiology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011409:Propylene Glycols / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects* / Q000276:immunology*; D012871:Skin Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D015848:Interleukin-5; D011409:Propylene Glycols; D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
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