Intravital observation of adhesion of lamina propria lymphocytes to microvessels of small intestine in mice.
OBJECTIVE
Although the recirculation of lymphocytes through the intestinal mucosa is important for the specific immune defense, the homing of lamina propria lymphocytes (LPLs) has not been clearly understood. The aim of this study is to compare, under an intravital microscope, the dynamic process of lymphocyte-endothelium recognition and binding in the murine intestinal mucosa of T lymphocytes from the lamina propria of intestine to that of T lymphocytes from the spleen.


METHODS
LPLs isolated from nonlymphoid areas of the small intestine and spleen (SPL) were fluorescence-labeled and injected into a jugular vein of recipient mice. Microvessels of the villus mucosa and ileal Peyer's patches were observed under an intravital fluorescence microscope, and the effects of anti-adhesion-molecule antibodies on lymphocyte-endothelial interaction were investigated.


RESULTS
LPLs accumulated abundantly in the microvessels of villus tips but not in the submucosal venules or postcapillary venules of Peyer's patches, where SPLs migrated selectively. The accumulation of LPLs in the villus tips was almost completely inhibited by anti-beta7-integrin and was significantly inhibited by anti-mucosal addressin cell-adhesion molecule 1 (MAdCAM-1) and anti-alpha4-integrin. Significant MAdCAM-1 expression was observed in the microvessels of the villus mucosa. Some SPLs adhered to the nonlymphoid mucosa, but most soon detached.


CONCLUSIONS
It was shown in vivo for the first time that T lymphocytes from the lamina propria but not from the spleen adhere selectively, mostly via alpha4beta7 and MAdCAM-1, to the microvessels of villus tips of the intestine, but not to the postcapillary venules of Peyer's patches.
Fujimori
Hitoshi
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Miura
Soichiro
S
Koseki
Seiichiro
S
Hokari
Ryota
R
Komoto
Shunsuke
S
Hara
Yuriko
Y
Hachimura
Satoshi
S
Kaminogawa
Shuichi
S
Ishii
Hiromasa
H
D000818:Animals; D000911:Antibodies, Monoclonal; D001485:Basement Membrane / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007136:Immunoglobulins / Q000032:analysis / Q000276:immunology; D007150:Immunohistochemistry; D016023:Integrins / Q000032:analysis / Q000276:immunology; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000737:chemistry / Q000276:immunology*; D019041:L-Selectin / Q000032:analysis / Q000276:immunology; D008208:Lymphatic System / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000276:immunology; D009088:Mucoproteins / Q000032:analysis / Q000276:immunology; D010581:Peyer's Patches / Q000098:blood supply / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; C071777:integrin alpha4beta7; D019041:L-Selectin