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Proteinase 3 expression on neutrophil membranes from patients with infectious disease
Takeshi Matsumoto1, Toshihiro Kaneko, Hideo Wada
1Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu City, Japan.
Abstract:
Proteinase-3 (PR3) is an abundant serine proteinase stored in the azurophilic granules of neutrophils and released to the cell surface upon activation where it contributes to local tissue destruction and inflammation. The sub-population of membrane PR3 (mPR3) high expression (PR3-high) varies among individuals. There are many reports about PR3 in Wegener's granulomatosis, but few about PR3 expression in patients with common inflammatory disorders, such as sepsis. The mPR3 expression on neutrophils from 56 patients with inflammatory disorders and from 64 healthy volunteers was examined by flow cytometry. High variability in the percentage of PR3-high (%PR3-high) neutrophils was observed in healthy volunteers and patients with inflammatory disease, and the %PR3-high was significantly greater in the patients (72 +/- 19% vs 55 +/- 20%, P < 0.0001). Overall neutrophil PR3 expression in patients with infectious diseases, especially systemic inflammatory response syndrome (SIRS) was significantly high (P < 0.01) and showed a positive correlation with C-reactive protein (CRP). Even under inflammatory conditions not involving autoimmune vasculitis, there are significant increases in both the absolute surface expression of PR3 and the numbers of neutrophils expressing high levels of PR3 and these correlate with CRP levels. The data are consistent with a model in which neutrophil membrane expression of PR3 is greatly influenced by an in vivo inflammatory environment.
Insights
Neutrophil membrane Proteinase-3 (PR3) expression increases in inflammatory disorders like sepsis. This elevated PR3 expression correlates with C-reactive protein levels, indicating its role in systemic inflammation.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Proteinase-3 (PR3) is a serine proteinase in neutrophil granules, implicated in tissue damage and inflammation.
- Membrane-bound PR3 (mPR3) expression varies, with high expression (PR3-high) noted in certain conditions.
- Limited research exists on PR3 expression in common inflammatory disorders beyond autoimmune vasculitis.
Purpose of the Study:
- To investigate membrane PR3 expression on neutrophils in patients with inflammatory disorders, including sepsis.
- To compare PR3 expression levels between patients and healthy individuals.
- To explore the correlation between PR3 expression and inflammatory markers like C-reactive protein (CRP).
Main Methods:
- Flow cytometry was used to quantify mPR3 expression on neutrophils.
- Neutrophils from 56 patients with inflammatory disorders and 64 healthy volunteers were analyzed.
- The percentage of PR3-high neutrophils (%PR3-high) and absolute PR3 expression were measured.
Main Results:
- A high variability in %PR3-high was observed in both healthy individuals and patients.
- Patients exhibited significantly higher %PR3-high compared to healthy volunteers (72% vs 55%, P < 0.0001).
- Elevated neutrophil PR3 expression, particularly in Systemic Inflammatory Response Syndrome (SIRS), correlated positively with CRP levels.
Conclusions:
- Neutrophil membrane PR3 expression is significantly increased in patients with inflammatory disorders, not limited to autoimmune vasculitis.
- The degree of PR3 expression on neutrophils is influenced by the in vivo inflammatory environment.
- Increased PR3 expression and %PR3-high neutrophils correlate with inflammatory markers like CRP.
