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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 CD15s was performed. CD15s 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 TNFαα‐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 TNFαα‐activated EC was increased (e.g. 0.9 dyn cm−2, P = 0.0061). CD15s induction in RASF was strongest in RA serum. Vimentin/CD15s 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 CD15s 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.

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Background Tissue destruction of the upper respiratory tract related to Granulomatosis with Polyangiitis (Wegener’s) – (GPA) which may result in stigmatizing lesions of the face is still poorly understood. Nasal biopsies that contain cartilage and/or bone to study the destruction process are difficult to obtain. Recent findings in a xenograft model of GPA in immunodeficient mice suggest that fibroblasts mediate at least in part this destruction of cartilage. Objectives To compare morphological and immunohistochemical features of destruction in GPA patients and GPA tissues xenografted into immunodeficient mice. Methods Nasal biopsies from GPA patients containing cartilage and/or bone fragments were evaluated for destruction by conventional histology. Cellular components, markers of differentiation and proliferation were characterized by immunohistochemistry (vimentin, CD68, TRAP, MMP 1-3-13, ALP, Osteonectin, CD 31, Ki-67). Xenografts of nasal mucosa from GPA patients with active endonasal disease and from sinusitis control patients were co- transplanted with healthy human cartilage in immunodeficient pfp/rag2 -/- mice and were investigated in parallel. Results Samples of nasal biopsies from GPA patients as well as xenografted GPA tissues show GPA related cartilage/bone destruction mediated by invading cells, not by ischemic necrosis due to vasculitis or areactive geographical necrosis. Invading cells in xenografts were identified as predominantly human fibroblast, while human tissues showed a more complex and variable pattern of cartilage/bone destruction. However, the morphology of destruction was very similar in tissue samples from both sources. Conclusions Nasal cartilage/bone destruction in GPA is an active process related to a broad spectrum of cells. However, fibroblasts are the dominant cartilage destructing cells both in GPA patients and in GPA xenografts, thus validating the findings in xenografts to be relevant for the human pathophysiology. Disclosure of Interest None Declared