Enamel matrix derivative promotes superoxide production and chemotaxis but reduces matrix metalloproteinase-8
Mamdouh M Karima1, Thomas E Van Dyke
1Department of Oral Basic and Clinical Sciences, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.
Background:
Polymorphonuclear leukocyte (PMN) is the predominant innate immune cell type activated in acute inflammation. The aim of this study is to determine the impact of enamel matrix derivative (EMD) on superoxide (O(2)(-)) generation, chemotaxis, and matrix metalloproteinase-8 (MMP-8) secretion by PMN in vitro to better understand the role of EMD in surgical wound healing.
Methods:
PMNs were isolated from healthy volunteers (n = 14). O(2)(-) generation was measured using a cytochrome c reduction assay. Chemotaxis was measured in a modified Boyden chamber. MMP-8 secretion was analyzed by Western blotting. A relative density method was used to determine the percentage of MMP-8 released from the PMNs in relation to the total cellular MMP-8 content.
Results:
O(2)(-) generation was significantly elevated when PMNs were stimulated with EMD (200 μg/mL) (P <0.01). Secondary stimulation of PMNs with 1 μM N-formyl-methionyl-leucyl-phenylalanine (fMLP) triggered earlier and more sustained O(2)(-) generation with EMD. EMD significantly increased PMN chemotactic activity (P <0.05). Combined stimulation with EMD plus fMLP resulted in significantly higher chemotaxis compared to fMLP alone (P <0.05). Conversely, EMD did not induce MMP-8 secretion from PMNs. MMP-8 secretion by PMNs in response to fMLP or serum-opsonized zymosan stimulation was significantly inhibited by EMD (P <0.05).
Conclusions:
EMD has specific, differential actions on PMNs that suggest potential for enhancement of wound healing, bacterial and tissue debris clearance (O(2)(-) generation and chemotaxis), and suppression of tissue damage and degradation (MMP-8 ). Together, the data suggest that EMD enhances wound healing and reduces inflammation.
Insights
Enamel matrix derivative (EMD) enhances polymorphonuclear leukocyte (PMN) activity, boosting superoxide generation and chemotaxis. EMD also suppresses matrix metalloproteinase-8 (MMP-8) secretion, indicating potential for improved wound healing and reduced inflammation.
Area of Science:
- Immunology
- Wound Healing Research
- Biomaterials Science
Background:
- Polymorphonuclear leukocytes (PMNs) are key innate immune cells in acute inflammation.
- Enamel matrix derivative (EMD) is being investigated for its role in surgical wound healing.
- Understanding EMD's effects on PMN function is crucial for optimizing wound repair.
Purpose of the Study:
- To investigate the impact of EMD on PMN superoxide (O(2)(-)) generation.
- To assess EMD's effect on PMN chemotaxis.
- To determine EMD's influence on matrix metalloproteinase-8 (MMP-8) secretion by PMNs.
Main Methods:
- PMNs isolated from healthy volunteers.
- Superoxide generation measured via cytochrome c reduction assay.
- Chemotaxis assessed using a modified Boyden chamber.
- MMP-8 secretion analyzed by Western blotting.
Main Results:
- EMD significantly elevated PMN superoxide generation, with enhanced and sustained responses upon secondary stimulation.
- EMD significantly increased PMN chemotactic activity, both alone and in combination with fMLP.
- EMD did not induce MMP-8 secretion but significantly inhibited fMLP- or zymosan-induced MMP-8 release.
Conclusions:
- EMD exhibits specific, differential effects on PMNs.
- EMD may enhance wound healing by promoting bacterial clearance and tissue debris removal via O(2)(-) generation and chemotaxis.
- EMD's suppression of MMP-8 suggests a role in reducing tissue damage and inflammation during wound healing.
Related Concept Videos
01:23Role of Matrix Metalloproteases in Degradation of ECM
A...
01:42The Extracellular Matrix
01:29The Extracellular Matrix
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
01:26Extracellular Matrix
01:38Inflammation