Cysteinyl leukotriene expression in chronic hyperplastic sinusitis-nasal polyposis: importance to eosinophilia and asthma.
BACKGROUND
Chronic hyperplastic eosinophilic sinusitis (CHS) results from the unregulated proliferation of eosinophils, T(H)2-like lymphocytes, goblet cells, mast cells, and fibroblasts and is present in most patients with asthma. The frequent coexpression of these disorders and their shared pathophysiology suggests that these are similar disorders affecting the upper and lower airways.


OBJECTIVE
We evaluated the expression of cysteinyl leukotrienes (CysLTs) in sinus tissue from subjects with CHS compared with that seen in healthy sinus tissue.


METHODS
Nasal polyp and sinus tissue was evaluated from 58 individuals undergoing elective functional endoscopic sinus surgery. The diagnosis of CHS was demonstrated through the presence of eosinophilia and activated (EG2(+)) eosinophils, as determined by means of tissue immunohistochemistry. Data were compared with those from both nasal polyp tissue without eosinophilic inflammation and healthy control sinus tissue obtained from the sinus ostiomeatal complex at the time of surgery for unrelated disorders. CysLTs were quantified by means of ELISA in lipid-extracted tissue. Activation of the metabolic pathway leading to CysLT synthesis was demonstrated by ribonuclease protection. Subjects were genotyped for leukotriene C(4) (LTC(4)) synthase C-to-A promoter polymorphism.


RESULTS
CysLT concentrations were significantly higher in tissue obtained from subjects with CHS (776.7 +/- 201.9 pg/g tissue) compared with that seen in healthy sinus tissue (355.7 +/- 101.6 pg/g tissue, P <.03). CysLT concentrations within noneosinophilic nasal polyps (328.0 +/- 116.4 pg/g tissue) were similar to those in control tissue. The presence of CysLTs in CHS was associated with increased expression of LTC(4) synthase mRNA. The C-to-A promoter polymorphism was associated with trends toward the increased presence of CHS and CysLTs.


CONCLUSIONS
CHS is characterized by the increased presence of CysLTs when compared with concentrations seen in tissue from patients with chronic inflammatory sinusitis or healthy sinus tissue. These studies support the use of LT modifiers as anti-inflammatory agents that might have clinical benefit in patients with these disorders.
Steinke
John W
JW
Asthma and Allergic Disease Center, Beirne Carter Center for Immunology, University of Virginia Health System, Charlottesville, VA 22908, USA.
Bradley
Dewayne
D
Arango
Pablo
P
Crouse
Charles D
CD
Frierson
Henry
H
Kountakis
Stilianos E
SE
Kraft
Monica
M
Borish
Larry
L
D000328:Adult; D001249:Asthma / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002908:Chronic Disease; D003545:Cysteine / Q000378:metabolism*; D004802:Eosinophilia / Q000235:genetics / Q000378:metabolism; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D006965:Hyperplasia; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012852:Sinusitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; D003545:Cysteine