Growth-related gene product α: A chemotactic cytokine for neutrophils in rheumatoid arthritis

A. E. Koch*, S. L. Kunkel, M. R. Shah, S. Hosaka, M. M. Halloran, G. K. Haines, M. D. Burdick, R. M. Pope, R. M. Strieter

*Corresponding author for this work

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

Leukocyte recruitment is critical in the inflammation seen in rheumatoid arthritis (RA). To determine whether the chemokine growth-related gene product α (groα) plays a role in this process, we examined synovial tissue (ST), synovial fluid (SF), and plasma samples from 102 patients with arthritis. RA SF contained more antigenic groα (mean 5.3 ± 1.9 ng/ml) than did SFs from either osteoarthritis (OA) or other forms of arthritis (mean 0.1 ng/ml) (p < 0.05). RA plasma contained more groα (mean 4.3 ± 1.8 ng/ml) than normal plasma (mean 0.1 ng/ml) (p < 0.05). RA ST fibroblasts (1.2 x 105/cells/ml RPMI 1640/24 h) produced antigenic groα (mean 0.2 ± 0.1 ng/ml), and this production was increased significantly upon incubation with TNF-α (mean 1.3 ± 0.3 ng/ml) or IL-1β (mean 2.3 ± 0.6 ng/ml) (p < 0.05). Cells from RA SF also produced groα: neutrophils (PMNs) (107 cells/ml/24 b) produced 3.7 ± 0.7 ng/ml. RA SF mononuclear cells produced groα, particularly upon incubation with LPS or PHA. Immunoreactive ST groα was found in greater numbers of RA compared with either OA or normal lining cells, as well as in RA compared with OA subsynovial macrophages (p < 0.05). IL-8 accounted for a mean of 36% of the RA SF chemotactic activity for PMNs, while epithelial neutrophil-activating peptide-78 accounted for 34%, and groα for 28%, of this activity. Combined neutralization of all three chemokines in RA SFs resulted in a mean decrease of 50% of the chemotactic activity for PMNs present in the RA SFs. These results indicate that groα plays an important role in the ingress of PMNs into the RA joint.

Original languageEnglish (US)
Pages (from-to)3660-3666
Number of pages7
JournalJournal of Immunology
Volume155
Issue number7
StatePublished - 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Koch, A. E., Kunkel, S. L., Shah, M. R., Hosaka, S., Halloran, M. M., Haines, G. K., Burdick, M. D., Pope, R. M., & Strieter, R. M. (1995). Growth-related gene product α: A chemotactic cytokine for neutrophils in rheumatoid arthritis. Journal of Immunology, 155(7), 3660-3666.