Luminal nitric oxide and epithelial expression of inducible and endothelial nitric oxide synthase in collagenous and lymphocytic colitis.
BACKGROUND
Colonic nitric oxide (NO) production in collagenous colitis (CC) has been studied in a small number of patients and found increased. The cellular source of NO is believed to be the colonic epithelial cells. The aim of this study was to investigate colonic NO levels in patients with CC and lymphocytic colitis (LC), to compare with the histopathological status and with the clinical activity, and to assess the epithelial expression of inducible and endothelial nitric oxide synthase (iNOS and eNOS).


METHODS
We included 19 patients with CC, 8 patients with LC and 15 controls. During colonoscopy, luminal gas was sampled and NO levels were measured using the chemiluminescence technique. Mucosal biopsies were obtained for routine histopathologic examination and immunohistochemical studies of iNOS and eNOS. Clinical activity, as measured by the mean frequency of daily bowel movements during the week prior to colonoscopy, was assessed.


RESULTS
Luminal NO levels, median (25-75 percentiles), in the patients with CC and LC were greatly increased compared to the controls, 1673 (145-8143) parts per billion (ppb) and 1838 (1065-2694) ppb versus 28 (20-46) ppb (P < 0.005, both). A positive association was seen between NO levels and histopathological status as well as clinical activity. Strong expression of iNOS was seen in the surface epithelium in 5 of 6 patients with CC and in 2 of 5 patients with LC.


CONCLUSIONS
The fact that luminal NO levels are related to histopathological status and correlate with clinical activity indicates that NO is involved in the pathophysiology of CC and LC. The epithelial cells are the most likely source of luminal NO.
Olesen
M
M
Dept. of Medicine, Division of Gastroenterology, Orebro University Hospital, Orebro, Sweden.
Middelveld
R
R
Bohr
J
J
Tysk
C
C
Lundberg
J O N
JO
Eriksson
S
S
Alving
K
K
Järnerot
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003092:Colitis / Q000201:enzymology* / Q000473:pathology; D003106:Colon / Q000201:enzymology* / Q000473:pathology; D003113:Colonoscopy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
D009569:Nitric Oxide; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III