Immunohistological and functional analysis of adhesion molecule expression in the rheumatoid synovial lining layer. Implications for synovial lining cell destruction.
OBJECTIVE
It has previously been shown that the adhesion of lymphocytes to microvascular endothelium mediates lymphocyte extravasation within inflamed synovium. After passing the endothelial barrier, binding of lymphocytes to matrix proteins and synovial lining cells may further lead to synovial membrane hyperplasia and subsequent cartilage destruction. Thus, we have explored the molecular basis of T cell-synovial lining cell interaction in the synovial membrane of patients with rheumatoid arthritis (RA).


METHODS
Using an immunohistochemical staining technique and an in vitro frozen section assay we studied the expression and the role of several adhesion molecules in T lymphocyte-synovial lining cell interaction in the inflamed synovial membrane.


RESULTS
In RA the macrophage-like (type A) synovial lining cells express high levels of intercellular adhesion molecule 1 [ICAM-1 (CD54)], whereas the fibroblast-like (type B) synovial lining cells predominantly express vascular cell adhesion molecule 1 (VCAM-1), in addition to moderate levels of ICAM-1. Both cell types express low levels of fibronectin. Unstimulated and anti-CD3 stimulated peripheral blood T cells bear the respective ligands lymphocyte function associated antigen 1 [LFA-1 (CD18/11a)], and very late antigen 4 and 5 [VLA-4 (CD29/49d) and VLA-5 (CD29/49e)]. T lymphocytes predominantly bound to type B synovial lining cells. Inhibition studies with monoclonal antibodies revealed that this binding involves the VLA-4/VCAM-1 and VLA-5/fibronectin (FN), but not the VLA-4/CS1 pathway. LFA-1 is also involved in this interaction via its ligand ICAM-1.


CONCLUSIONS
These results show that the molecular basis of T lymphocyte binding to rheumatoid synovial lining cells is different from that described for T lymphocyte binding to synovial membrane vascular endothelium which involves the VLA-4/VCAM-1 and VLA-4/CS-1 pathways, but not the LFA-1/ICAM-1 pathway.
van Dinther-Janssen
A C
AC
Department of Pathology, Free University and Slotervaart Hospital, Amsterdam, The Netherlands.
Kraal
G
G
van Soesbergen
R M
RM
Scheper
R J
RJ
Meijer
C J
CJ
D000911:Antibodies, Monoclonal; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000276:immunology / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D016029:Receptors, Very Late Antigen / Q000032:analysis / Q000276:immunology / Q000502:physiology; D013583:Synovial Membrane / Q000098:blood supply / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D036341:Intercellular Signaling Peptides and Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D010455:Peptides; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; C076687:CS1 peptide; D018799:Intercellular Adhesion Molecule-1