Role of sphingosine 1-phosphate receptor expression in eosinophils of patients with allergic rhinitis, and effect of topical nasal steroid treatment on this receptor expression.
OBJECTIVE
Recent research has indicated that sphingosine 1-phosphate plays a role in allergy. This study examined the effect of allergen challenge on the expression of sphingosine 1-phosphate receptors on the eosinophils of allergic rhinitis patients, and the effect of steroid treatment on this expression.


METHODS
A prospective, non-randomised study.


METHODS
The study had three parts. Firstly, sphingosine 1-phosphate receptor expression on the eosinophils of allergic rhinitis patients and control patients was determined. Secondly, sphingosine 1-phosphate receptor expression was quantified pre- and post-allergen challenge, before and after a short course of fluticasone propionate; all patients underwent symptom scoring and peak nasal inspiratory flow measurement pre- and post-allergen challenge, both before and after steroid or saline treatment. Thirdly, the effect of sphingosine 1-phosphate on eosinophil migration was examined.


RESULTS
The eosinophils of both allergic rhinitis patients and controls expressed sphingosine 1-phosphate1, 3, 4, and 5. Eosinophils from all allergic rhinitis patients demonstrated up-regulation in sphingosine 1-phosphate expression after allergen challenge. These changes were statistically very significant for sphingosine 1-phosphate1, 4, and 5, and moderately significant for sphingosine 1-phosphate3. Sphingosine 1-phosphate receptor expression up-regulation was abolished in the steroid-treated group after allergen challenge; however, the saline-treated group showed no change in sphingosine 1-phosphate receptor expression after allergen challenge. Peak nasal inspiratory flow scores were significantly diminished after allergen challenge prior to treatment, but not after a course of topical nasal steroids. Sphingosine 1-phosphate induced eosinophil chemotaxis was increased following allergen challenge in allergic rhinitis subjects.


CONCLUSIONS
Local intranasal steroid therapy acts directly to block allergen-induced up-regulation of sphingosine 1-phosphate receptors on the peripheral eosinophils of allergic rhinitis patients, and this is coincident with post-challenge peak nasal inspiratory flow measurement improvements. These observations support the idea that such an increase in sphingosine 1-phosphate receptor expression is clinically relevant in allergic rhinitis, with potential consequences for eosinophil migration and survival.
Mackle
T
T
Department of Otorhinolaryngology, Beaumont Hospital, Dublin, Ireland. Mackle_tara@hotmail.com
Gendy
S S
SS
Walsh
M
M
McConn-Walsh
R
R
Costello
R W
RW
Walsh
M-T
MT
D000287:Administration, Topical; D000328:Adult; D000730:Androstadienes / Q000627:therapeutic use; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D000068298:Fluticasone; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009299:Nasal Provocation Tests; D011446:Prospective Studies; D049349:Receptors, Lysosphingolipid / Q000008:administration & dosage / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy / Q000378:metabolism*; D013256:Steroids / Q000008:administration & dosage; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
D000730:Androstadienes; D049349:Receptors, Lysosphingolipid; D013256:Steroids; D000068298:Fluticasone