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Interactions between rheumatoid arthritis synovial fibroblast migration and endothelial cells
Author(s) -
ZimmermannGeller Birgit,
Köppert Sina,
Kesel Nina,
Hasseli Rebecca,
Ullrich Sebastian,
Lefèvre Stephanie,
Frommer Klaus,
Gehrke Thorsten,
Schönburg Markus,
Rehart Stephan,
Schumacher Udo,
MüllerLadner Ulf,
Neumann Elena
Publication year - 2019
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12208
Subject(s) - selectin , cell adhesion molecule , adhesion , cell adhesion , microbiology and biotechnology , tumor necrosis factor alpha , e selectin , chemistry , fibronectin , synovial fluid , umbilical vein , immunology , medicine , cell , pathology , biology , osteoarthritis , biochemistry , in vitro , alternative medicine , organic chemistry
Leukocytes travel within the circulation and enter connective tissues by interactions with endothelium of postcapillary venules mediated by cell adhesion molecules, summarized as the leukocyte adhesion cascade. In the severe combined immunodeficient ( SCID ) mouse model, rheumatoid arthritis ( RA ) synovial fibroblasts ( SF ) migrated to distant cartilage through the vasculature. Therefore, RASF adhesion toward endothelial cells ( EC ) and E‐ and P‐selectins were analyzed. Cell‐to‐cell binding assays between SF and EC were performed. Interactions of SF with tumor necrosis factor α (TNFα)‐activated EC or selectins were analyzed in flow adhesion assays. Immunohistochemistry for E‐selectin ligand CD 15s was performed. CD 15s induction in RASF by human serum or media was evaluated. Wild‐type and E ‐/‐/ P ‐/‐ Selectin‐ SCID mice were used for inverse‐wrap surgery. After laser‐mediated microdissection, real‐time PCR for E‐/P‐selectin/vascular cell adhesion molecule 1 was performed. Adhesion between SF / EC under static conditions was highest in Roswell Park Memorial Institute‐cultured RASF to TNFα α‐activated human umbilical vein endothelial cells (2.25‐fold) and RASF adhesion was higher toward venous than arterial EC (Dulbecco's modified eagle medium P = 0.0419, RPMI P = 0.0119). In flow chamber assays, RASF adhesion to E‐selectin was higher than to P‐selectin (e.g. 0.9 dyn cm −2 P = 0.0001). Osteoarthritis synovial fibroblasts showed lower rolling/adhesion properties (e.g. 0.5 dyn cm −2 , P = 0.0010). RASF adhesion to TNFα α‐activated EC was increased (e.g. 0.9 dyn cm −2 , P = 0.0061). CD 15s induction in RASF was strongest in RA serum. Vimentin/ CD 15s double‐positive cells were detectable. In E‐/P‐selectin‐deficient mice, contralateral invasion was reduced ( P = 0.023). E‐ and P‐selectin, and vascular cell adhesion molecule 1 expression in EC of implants was confirmed. Our data indicate that the milieu within vessels induces CD 15s which enables RASF to interact with E‐selectin/ EC under flow. Therefore, RASF may migrate to distant sites and leave the vasculature similarly to leukocytes.