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Matrix metalloproteinase-8 in sera and from polymorphonuclear leucocytes in rheumatoid arthritis: in vitro
L Rajasekhar1, L B Liou, C Y Chan
1Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Tao-yuan County, Taiwan.
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.
Insights
Immune complexes stimulate matrix metalloproteinase-8 (MMP-8) secretion from polymorphonuclear leucocytes (PMNs) in rheumatoid arthritis (RA) patients and controls. Serum MMP-8 may indicate acute inflammatory activity, correlating with C-reactive protein (CRP).
Area of Science:
- Immunology
- Biochemistry
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation.
- Matrix metalloproteinase-8 (MMP-8) is implicated in inflammatory processes.
- Polymorphonuclear leucocytes (PMNs) are key immune cells involved in inflammation.
Purpose of the Study:
- To investigate MMP-8 secretion from RA PMNs in response to immune complexes (IC) and cytokines.
- To explore the correlation between serum MMP-8 levels and disease activity in RA patients.
Main Methods:
- PMNs from RA patients and healthy controls were stimulated in vitro with various agents, including IC, cytokines (IL-15, IL-18), and phorbol myristate acetate (PMA).
- MMP-8 levels in cell supernatants and patient sera were quantified using ELISA.
- Serum MMP-8 levels were correlated with disease activity scores and C-reactive protein (CRP).
Main Results:
- Immune complexes significantly induced MMP-8 secretion from both control and RA PMNs.
- Anti-human immunoglobulin G (anti-HIgG) and its fragments strongly elicited MMP-8 secretion, suggesting an Fc receptor-independent mechanism.
- IL-18 combined with PMA significantly increased MMP-8 secretion from RA PMNs.
- Serum MMP-8 positively correlated with serum CRP, indicating a link to acute inflammation.
Conclusions:
- Immune complexes are potent stimulators of MMP-8 secretion from PMNs.
- RA PMNs showed enhanced MMP-8 secretion in response to IL-18 and PMA combination.
- Serum MMP-8 may serve as a biomarker for acute inflammatory activity in RA.
