Aberrant binding of lamina propria lymphocytes to vascular endothelium in inflammatory bowel diseases.
OBJECTIVE
Lymphocyte recirculation between the blood and lymphoid tissues as well as lymphocyte migration into inflammatory sites are controlled by lymphocyte interaction with vascular endothelium. The aim of this study was to compare the endothelial binding mechanisms of lamina propria lymphocytes (LPL) isolated from normal and inflamed bowel.


METHODS
Binding of LPL from normal and inflamed (inflammatory bowel disease) bowel to endothelium was studied using an in vitro binding assay. Expression of adhesion molecules on LPL and on mucosal endothelial cells was analyzed by flow cytometry and immunohistochemistry.


RESULTS
In inflammatory bowel disease, the selectivity of lymphocyte-endothelial interaction was lost, i.e., immunoblasts bound well not only to mucosal vessels but also to peripheral lymph node venules. The set of homing receptors expressed on mucosal immunoblasts did not directly predict the endothelial binding properties of these cells; e.g., L-selectin-negative blasts adhered well to lymph node vessels using peripheral lymph node-specific endothelial adhesion antigen (PNAd). PNAd was aberrantly expressed in vessels in the inflamed mucosa, where it also mediated LPL binding.


CONCLUSIONS
These findings are important in understanding the physiology of lymphocyte homing into the gut and suggest an important role for PNAd in the pathogenesis of inflammatory bowel disease.
Salmi
M
M
Department of Medical Microbiology, University of Turku, Finland.
Granfors
K
K
MacDermott
R
R
Jalkanen
S
S
D000954:Antigens, Surface / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000473:pathology / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D007422:Intestines / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D008214:Lymphocytes / Q000502:physiology*; D008565:Membrane Proteins; D014699:Venules / Q000503:physiopathology
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; C069886:L-selectin counter-receptors; D008565:Membrane Proteins