Nitric oxide modulates T-lymphocyte migration in Peyer's patches and villous submucosa of rat small intestine.
OBJECTIVE
Although nitric oxide (NO) is known to influence the recruitment of neutrophils in inflamed tissue, its role in lymphocyte-endothelial cell interactions remains poorly understood. The objectives of this study were to assess the effects of NO synthesis inhibition on T-lymphocyte migration in microvessels of rat small intestine and to define the role of adhesion molecules in this process.


METHODS
T lymphocytes collected from rat intestinal lymph were labeled with carboxyfluorescein diacetate succinimidyl ester and injected into the jugular vein of recipient rats. The migration of T lymphocytes into normal and NG-nitro-L-arginine methyl ester (L-NAME)-treated intestinal microvessels was monitored by using an intravital microscope.


RESULTS
L-NAME significantly increased rolling and adherence of lymphocytes in postcapillary venules of Peyer's patches and submucosal venules without significantly decreasing red blood cell velocity. The subsequent appearance of lymphocytes in the initial lymphatics was also accelerated by L-NAME. Anti-4-integrin antibody markedly inhibited the L-NAME-induced lymphocyte-endothelial cell interaction. Anti-P-selectin monoclonal antibody also significantly attenuated these adhesive interactions in both vascular regions.


CONCLUSIONS
These data suggest that NO is an important modulator of lymphocyte migration in Peyer's patches and in nonlymphoid regions of the intestine.
Hokari
R
R
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Miura
S
S
Fujimori
H
H
Tsuzuki
Y
Y
Shigematsu
T
T
Higuchi
H
H
Kimura
H
H
Kurose
I
I
Serizawa
H
H
Suematsu
M
M
Yagita
H
H
Granger
D N
DN
Ishii
H
H
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006146:Guanidines / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000098:blood supply / Q000502:physiology; D008196:Lymph / Q000166:cytology / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010581:Peyer's Patches / Q000098:blood supply* / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D013388:Succinimides; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D014699:Venules / Q000187:drug effects / Q000502:physiology
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D004791:Enzyme Inhibitors; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006146:Guanidines; D013388:Succinimides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester