Evidence that 13-14 di-hydro, 15-keto prostaglandin D(2)-induced airway eosinophilia in guinea-pigs is independent of interleukin-5.
OBJECTIVE
Prostaglandin D(2) (PGD(2)) has been shown to cause eosinophil, basophil and Th2 cell chemotaxis in vitro and in vivo through an action on the prostaglandin CRTH2 receptor. In the present study, the dependence of PGD(2)-induced eosinophil accumulation in vivo on interleukin-5 (IL-5) blood eosinophilia was investigated.


METHODS
Guinea-pigs were exposed to aerosols of 13,14di-hydro 15-keto PGD(2) (DK-PGD(2)) or platelet activating factor (PAF) and the eosinophil content of the bronchoalveolar lavage fluid or blood determined. In some experiments, DK-PGD(2) was administered systemically and eosinophilia measured.


RESULTS
Aerosols of DK-PGD(2) caused eosinophil accumulation in the lungs 24h after exposure. DK-PGD(2) (10 microg x ml(-1)) -induced airway eosinophilia was inhibited when animals were treated with the CRTH2 receptor antagonist ramatroban. 1-4h after exposure to DK-PGD(2) a significant decrease in blood eosinophil count was measured. The anti-IL-5 antibody TRFK-5 had no inhibitory effect of DK-PGD(2)-induced airway eosinophilia, but abolished airway eosinophilia induced by exposure of guinea-pigs to aerosols of PAF. Intracardiac injection of DK-PGD(2) induced a dose-related increase in blood eosinophil numbers.


CONCLUSIONS
It is concluded that, in the guinea-pig, DK-PGD(2)-induced airway eosinophilia is mediated by an action on prostaglandin CRTH2 receptors and that this response appears to be independent of IL-5.
Whelan
C J
CJ
Department of Life Sciences, University of Hertfordshire, Hertfordshire, UK. c.j.whelan@herts.ac.uk
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D004802:Eosinophilia / Q000139:chemically induced*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D015848:Interleukin-5 / Q000276:immunology*; D008168:Lung / Q000187:drug effects / Q000276:immunology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000819:agonists / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
D002227:Carbazoles; D015848:Interleukin-5; D010975:Platelet Aggregation Inhibitors; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; C063119:ramatroban; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor