Endotoxin stimulates lymphocyte-endothelial interactions in rat intestinal Peyer's patches and villus mucosa.
Although lymphocyte-endothelial cell interactions represent a key step in controlling the recruitment of lymphocytes into gut-associated tissues, its dynamic process in microvessels of lymphoid (Peyer's patches) and nonlymphoid (villus) regions of the small bowel remains poorly understood. We monitored the migration of fluorescence-labeled T lymphocytes into normal and lipopolysaccharide (LPS)-inflamed rat intestinal microvessels using intravital microscopy. In Peyer's patches, T lymphocytes selectively adhered to postcapillary venules, although such selectivity was not observed in submucosal venules of villi. T lymphocytes exhibited rolling behavior followed by firm adhesion in microvessels of both the Peyer's patches and the villi, with both types of adhesive interaction being mediated by alpha 4-integrins. The enhanced rolling and adherence of lymphocytes observed in Peyer's patches and submucosal venules of villi of LPS-treated rats were preceded by a reduction in shear rate and were mediated largely by alpha 4-integrins and partly by beta 2-integrins. In capillaries of intestinal mucosa, lymphocyte adherence occurred without rolling and was independent of alpha 4-integrins. LPS also significantly increased adherence of lymphocytes to villus capillaries, which was not mediated by either alpha 4- or beta 2-integrin. These observations demonstrate significant heterogeneity of lymphocyte-endothelial cell interactions within different regions of the intestinal mucosa.
Miura
S
S
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Tsuzuki
Y
Y
Kurose
I
I
Suematsu
M
M
Shigematsu
T
T
Kimura
H
H
Higuchi
H
H
Serizawa
H
H
Yagita
H
H
Okumura
K
K
Granger
D N
DN
Ishii
H
H
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology*; D039441:Integrin alpha4; D007413:Intestinal Mucosa / Q000098:blood supply*; D007421:Intestine, Small / Q000098:blood supply*; D008297:Male; D008871:Microvilli / Q000502:physiology; D010581:Peyer's Patches / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013601:T-Lymphocytes / Q000502:physiology*; D014657:Vasculitis / Q000503:physiopathology
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D004731:Endotoxins; D039441:Integrin alpha4