Matrix metalloproteinase-8 in sera and from polymorphonuclear leucocytes in rheumatoid arthritis: In vitro characterization and correlation with disease activity

L. Rajasekhar, L.-B. Liou, C.Y. Chan, W.-P. Tsai, C.Y. Cheng

Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Tao-yuan County, Taiwan

ABSTRACT
Objectives
To determine matrix metalloproteinase- 8 (MMP-8) secretion from rheumatoid arthritis (RA) peripheral blood polymorphonuclear leucocytes (PMNs), in response to immune complexes (IC), cytokines and their combinations, and to study correlation of serum MMP-8 with disease activity.

Methods
PMNs from RA patients and controls were stimulated in vitro with interleukin -15 (IL-15), IL-18, adherent immune complexes, rabbit anti-human immunoglobulin G (anti-HIgG), human immunoglobulin G (HIgG), and their F (ab') 2 prongs, phorbol myristate acetate (PMA) or combinations of above. Supernatants from these experiments and sera from both groups were assayed for MMP-8 using ELISA and correlated with disease activity measures in patients.

Results
MMP-8 secretion from stimulated PMNs was compared to unstimulated PMNs. Immune complexes elicited significant MMP-8 secretion (p = 0.006 and 0.001, control and RA respectively). Unlike HIgG and its F (ab')2 fragment, very high secretion was elicited by anti-HIgG (242.37 10.85 ng/ml ) and its F (ab')2 prong (195.85 28.67 ng/ml). IL-15 did not elicit any secretion. IL-18 with PMA increased secretion significantly only from RA PMNs (p = 0.003). Serum MMP-8 correlated positively with serum CRP (p = 0.017) and not with disease activity score (p = 0.199).

Conclusions
We for the first time demonstrate that immune complexes elicit MMP-8 secretion from PMNs. Except for higher secretion from RA PMNs in response to combination of IL-18 and PMA, both control and RA PMNs respond similarly to various stimuli. Secretion by anti-HIgG occurs by a mechanism independent of Fc receptor. Correlation with CRP suggest that serum MMP-8 may be an indicator of acute inflammatory activity.

Key words
Matrix metalloproteinase-8, rheumatoid arthritis, immune complexes, cytokines.


This study was supported by the National Science Council, Taiwan (ROC) (NSC 88-2314-B-182A-003, NSC 89-2314B-182A-032, NSC 89-2314-B-182A-126) and in part by Chang Gung Memorial Hospital.
Present address of Liza Rajasekhar: Division of Rheumatology, Nizam's Institute of Medical Sciences, Hyderabad, India; supported by Chang Gung Memorial Hospital, Lin-kou.
Please address correspondence and reprint requests to: Lieh-Bang Liou, MD, PhD, Chief, Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, 5, Fu-shin Street, Kwei-san Hsiang, Tao-yuan County, Taiwan 333. 
E-mail: b890121@adm.cgmh.org.tw

Clin Exp Rheumatol 2004; 22: 597-602.
Copyright Clinical and Experimental Rheumatology 2004.