In:
The Journal of Immunology, The American Association of Immunologists, Vol. 196, No. 1_Supplement ( 2016-05-01), p. 203.21-203.21
Abstract:
Cobalt chrome (CoCr) is a major component of orthopaedic implants and a source of metallic wear debris, which may contribute to harmful inflammation and implant failure. Intra-peritoneal inoculation of CoCr induces a robust innate type 2 response with increases in M2 macrophages, eosinophils, and neutrophils and this response is dependent on Spleen tyrosine kinase (SYK) and Bruton’s tyrosine kinase (BTK) signaling, but not TLR, Caspase-1, or Cyclooxygenase signaling. We have also shown that this robust response is independent of T and B cell signaling. To examine this response in a more clinically relevant murine model, bilateral intra-articular knee injections of CoCr microparticles were given to C57BL/6 mice and changes in different innate immune cells were assessed from knee synovial cell isolates. Administration of the SYK inhibitor BAY 61-3606, or the BTK inhibitor Ibrutinib, abrogated innate immune cell recruitment and M2 macrophage polarization which is otherwise observed 2 days after inoculation with CoCr microparticles. The presence of M2 macrophages (CD68+, CD206+, and CD163+) is also observed in human peri-prosthetic tissue samples obtained from patients undergoing revision joint arthroplasty. Taken together, our findings suggest that BTK signaling is required for the type 2 inflammatory response to CoCr microparticles, providing a potential novel target for control of harmful inflammation leading to fibrosis and aseptic loosening.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.196.Supp.203.21
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2016
detail.hit.zdb_id:
1475085-5
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