Antigen-presenting cells containing bacterial peptidoglycan in synovial tissues of rheumatoid arthritis patients coexpress costimulatory molecules and cytokines.
OBJECTIVE
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by intimal lining hyperplasia and massive infiltration of the synovial sublining by antigen-presenting cells (APCs), lymphocytes, and plasma cells. Peptidoglycan (PG), a major cell wall component of gram-positive bacteria, which is abundantly expressed in all mucosa, is believed to be involved in the pathogenesis of RA because of its ability to induce the production of proinflammatory cytokines as well as to induce arthritis in rodents. While PG has been detected in APCs in RA joints, little is known about the role of these cells in RA. In this study, the presence and immune competence of PG-containing cells in synovial tissues from 14 RA and 14 osteoarthritis (OA) patients were analyzed in situ.


METHODS
Using immunohistochemistry, we examined the coexpression of phenotypic markers, costimulatory molecules, and cytokines by PG-containing cells.


RESULTS
PG was present in higher numbers in RA than in OA synovial tissues, although the difference was not significant. PG-containing cells were mainly macrophages, but some mature dendritic cells also contained PG. A high percentage of PG-containing cells in both RA and OA synovial tissues coexpressed HLA-DR. CD40, CD80, and CD86 expression by PG-containing cells was higher in RA than in OA tissues. Furthermore, PG-containing cells coexpressed cytokines, which modulate inflammatory reactions, in particular, tumor necrosis factor alpha and interleukins 6 and 10.


CONCLUSIONS
The results suggest that PG-containing cells may contribute to inflammation within the microenvironment of the joint in RA patients.
Schrijver
I A
IA
Erasmus University Rotterdam, The Netherlands.
Melief
M J
MJ
Tak
P P
PP
Hazenberg
M P
MP
Laman
J D
JD
D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000737:chemistry* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006094:Gram-Positive Bacteria / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000473:pathology; D010457:Peptidoglycan / Q000032:analysis* / Q000235:genetics; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology*
D018122:B7-1 Antigen; D015415:Biomarkers; D016207:Cytokines; D010457:Peptidoglycan