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pubmed:abstractText |
The leukocyte activation marker CD69 functions as a negative regulator of the immune response, both in NK-dependent tumor rejection and in the inflammation associated with lymphocyte-dependent collagen-induced arthritis. In contrast, it has been reported that CD69-deficient mice are refractory to the neutrophil-dependent acute inflammatory response associated with anti-type II collagen antibody-induced arthritis (CAIA), suggesting a positive regulatory role for CD69 in neutrophil function during arthritis induction. To clarify this discrepancy, the CAIA response was independently analyzed in our CD69-deficient mice. In these experiments, the inflammatory response was unaffected by CD69 deficiency. Additionally, the in vivo down-regulation of CD69 expression by treatment of wild-type mice with the anti-CD69 mAb 2.2, which mimics the CD69-deficient phenotype, did not affect the course of arthritis in this model. Moreover, down-regulation of CD69 expression increased expression in arthritic joints of key inflammatory mediators, including IL-1beta, IL-6 and the chemokine MCP-1. Neutrophil accumulation in zymosan-treated air pouches and in thioglycolate-treated peritoneal cavities was also unaffected in CD69-deficient mice. In addition, CD69 expression was absent in activated neutrophils. Taken together, these results rule out a significant stimulatory role for CD69 in acute inflammatory responses mediated by neutrophils.
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