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Stromal cell-derived factor 1 (CXCL12) induces monocyte migration into human synovium transplanted onto SCID Mice.
Arthritis Rheum. 2002 Mar; 46(3):824-36.AR

Abstract

OBJECTIVE

The mechanisms by which monocyte/macrophage cells migrate to the joint involve a series of integrated adhesion and signaling events in which chemokines and their receptors are strongly implicated. This study was undertaken to investigate the hypothesis that stromal cell-derived factor 1 (SDF-1), a CXC chemokine (CXCL12), plays a critical role in monocyte/macrophage localization to synovium.

METHODS

SDF-1 and CXC receptor 4 (CXCR4) expression in rheumatoid arthritis (RA) and osteoarthritis synovium and graft SDF-1, tumor necrosis factor alpha (TNF alpha), and human and murine vascular markers were examined by immunohistochemistry and double-immunofluorescence. The functional capacity of SDF-1 to modulate monocyte migration into joints was investigated by examining the localization of pro-myelomonocytic U937 cells into synovial tissue transplanted into SCID mice. SDF-1, TNF alpha, or saline was injected into graft sites and response determined by the number of fluorescently labeled U937 cells (injected intravenously) detected in grafts by ultraviolet microscopy.

RESULTS

SDF-1 and CXCR4 were highly expressed in CD68+ cells in the RA synovium. SDF-1 induced U937 cell migration in vitro and in vivo in a dose-dependent manner and, in vivo, SDF-1 was more effective than TNF alpha. In contrast to TNF alpha, SDF-1 did not induce intracellular adhesion molecule 1 in transplant microvasculature. Furthermore, intragraft injection of SDF-1 did not up-regulate TNF alpha, or vice versa.

CONCLUSION

This study demonstrates, for the first time, that SDF-1 is functional in vivo when injected into synovial grafts. In addition, SDF-1 is more potent than TNF alpha, and its mechanisms of action appear to be autonomous. Therefore, SDF-1 may be an important TNF-independent molecule involved in the migration to and retention of inflammatory effector cells in the joint.

Authors+Show Affiliations

Guy's, St Thomas and King's College School of Medicine, London, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11920421

Citation

Blades, M C., et al. "Stromal Cell-derived Factor 1 (CXCL12) Induces Monocyte Migration Into Human Synovium Transplanted Onto SCID Mice." Arthritis and Rheumatism, vol. 46, no. 3, 2002, pp. 824-36.
Blades MC, Ingegnoli F, Wheller SK, et al. Stromal cell-derived factor 1 (CXCL12) induces monocyte migration into human synovium transplanted onto SCID Mice. Arthritis Rheum. 2002;46(3):824-36.
Blades, M. C., Ingegnoli, F., Wheller, S. K., Manzo, A., Wahid, S., Panayi, G. S., Perretti, M., & Pitzalis, C. (2002). Stromal cell-derived factor 1 (CXCL12) induces monocyte migration into human synovium transplanted onto SCID Mice. Arthritis and Rheumatism, 46(3), 824-36.
Blades MC, et al. Stromal Cell-derived Factor 1 (CXCL12) Induces Monocyte Migration Into Human Synovium Transplanted Onto SCID Mice. Arthritis Rheum. 2002;46(3):824-36. PubMed PMID: 11920421.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stromal cell-derived factor 1 (CXCL12) induces monocyte migration into human synovium transplanted onto SCID Mice. AU - Blades,M C, AU - Ingegnoli,F, AU - Wheller,S K, AU - Manzo,A, AU - Wahid,S, AU - Panayi,G S, AU - Perretti,M, AU - Pitzalis,C, PY - 2002/3/29/pubmed PY - 2002/4/16/medline PY - 2002/3/29/entrez SP - 824 EP - 36 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 46 IS - 3 N2 - OBJECTIVE: The mechanisms by which monocyte/macrophage cells migrate to the joint involve a series of integrated adhesion and signaling events in which chemokines and their receptors are strongly implicated. This study was undertaken to investigate the hypothesis that stromal cell-derived factor 1 (SDF-1), a CXC chemokine (CXCL12), plays a critical role in monocyte/macrophage localization to synovium. METHODS: SDF-1 and CXC receptor 4 (CXCR4) expression in rheumatoid arthritis (RA) and osteoarthritis synovium and graft SDF-1, tumor necrosis factor alpha (TNF alpha), and human and murine vascular markers were examined by immunohistochemistry and double-immunofluorescence. The functional capacity of SDF-1 to modulate monocyte migration into joints was investigated by examining the localization of pro-myelomonocytic U937 cells into synovial tissue transplanted into SCID mice. SDF-1, TNF alpha, or saline was injected into graft sites and response determined by the number of fluorescently labeled U937 cells (injected intravenously) detected in grafts by ultraviolet microscopy. RESULTS: SDF-1 and CXCR4 were highly expressed in CD68+ cells in the RA synovium. SDF-1 induced U937 cell migration in vitro and in vivo in a dose-dependent manner and, in vivo, SDF-1 was more effective than TNF alpha. In contrast to TNF alpha, SDF-1 did not induce intracellular adhesion molecule 1 in transplant microvasculature. Furthermore, intragraft injection of SDF-1 did not up-regulate TNF alpha, or vice versa. CONCLUSION: This study demonstrates, for the first time, that SDF-1 is functional in vivo when injected into synovial grafts. In addition, SDF-1 is more potent than TNF alpha, and its mechanisms of action appear to be autonomous. Therefore, SDF-1 may be an important TNF-independent molecule involved in the migration to and retention of inflammatory effector cells in the joint. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/11920421/Stromal_cell_derived_factor_1__CXCL12__induces_monocyte_migration_into_human_synovium_transplanted_onto_SCID_Mice_ L2 - https://doi.org/10.1002/art.10102 DB - PRIME DP - Unbound Medicine ER -