Prostaglandin D2 reinforces Th2 type inflammatory responses of airways to low-dose antigen through bronchial expression of macrophage-derived chemokine.
PGD2, a lipid mediator released from mast cells, is known to participate in allergic reactions. However, the mechanism by which PGD2 contributes to such reactions remains unclear. We established a novel experimental model of asthma that permitted direct assessment of the role of PGD2 in airway inflammation. Antigen-sensitized mice were exposed to aerosolized prostaglandin D2 (PGD2) 1 d before challenge with low-dose aerosolized antigen. Not only the numbers of eosinophils, lymphocytes, and macrophages but also the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid were higher in PGD2-pretreated mice than in control mice. The expression of macrophage-derived chemokine (MDC), a chemoattractant for Th2 cells, was greater in PGD2-pretreated mice than in control. Injection of anti-MDC antibody into PGD2-pretreated mice markedly inhibited inflammatory cell infiltration as well as Th2 cyto-kine production after antigen challenge. These results indicate that PGD2 accelerates Th2 type inflammation by induction of MDC. Our results suggest that this mechanism may play a key role in the development of human asthma and that MDC might be a target molecule for therapeutic intervention.
Honda
Kyoko
K
Deptartment of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Mibu-machi Shimotsuga-gun, Tochigi 321-0293, Japan.
Arima
Masafumi
M
Cheng
Gang
G
Taki
Shinsuke
S
Hirata
Hirokuni
H
Eda
Fukiko
F
Fukushima
Fumiya
F
Yamaguchi
Bunpei
B
Hatano
Masahiko
M
Tokuhisa
Takeshi
T
Fukuda
Takeshi
T
D000818:Animals; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002460:Cell Line; D054422:Chemokine CCL22; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015230:Prostaglandin D2 / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; C515482:CCL22 protein, human; C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D015230:Prostaglandin D2