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Bimodal distribution of proteinase 3 (PR3) surface expression reflects a constitutive heterogeneity in the
L Halbwachs-Mecarelli1, G Bessou, P Lesavre
1INSERM U90, Hôpital Necker, Paris, France.
Abstract:
Proteinase 3, which is known as an intracellular serine protease of neutrophils, was detected at the surface of a subpopulation of freshly isolated PMN. The proportion of PR3-positive and -negative PMN, observed by flow cytometry with anti-PR3 mAbs or ANCA autoantibodies, varies among individuals but is extremely stable for each individual over prolonged time periods. After PMN degranulation by FMLP with cyt. B, membrane PR3 expression increases but the proportion of low and high PR3-expressing cells remains stable. The existence of a subset of PMN which spontaneously expresses PR3 and varies among individuals, may be relevant to the pathogenesis of anti-PR3 ANCA autoantibody-related vasculitis.
Insights
Proteinase 3 (PR3) is found on neutrophils, with varying levels between individuals. This cell surface expression is stable over time and may play a role in anti-PR3 ANCA-associated vasculitis.
Area of Science:
- Immunology
- Cell Biology
- Protease Research
Background:
- Proteinase 3 (PR3) is an intracellular serine protease primarily found within neutrophils.
- Neutrophils play a critical role in the innate immune system and inflammatory responses.
- Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of autoimmune diseases.
Purpose of the Study:
- To investigate the surface expression of Proteinase 3 (PR3) on neutrophils.
- To determine the stability and variability of PR3 expression on neutrophils.
- To explore the potential relevance of PR3 surface expression in anti-PR3 ANCA autoantibody-related vasculitis.
Main Methods:
- Flow cytometry was used to detect PR3 on the surface of freshly isolated polymorphonuclear cells (PMN).
- Anti-PR3 monoclonal antibodies (mAbs) and ANCA autoantibodies were utilized for detection.
- PMN degranulation was induced using formyl-methionyl-leucyl-phenylalanine (fMLP) and cytochalasin B (Cyt B).
Main Results:
- Proteinase 3 (PR3) was detected on the surface of a subpopulation of freshly isolated PMN.
- The proportion of PR3-positive and -negative PMN varied among individuals but remained stable for each individual over time.
- While PMN degranulation increased membrane PR3 expression, the relative proportions of low and high PR3-expressing cells were maintained.
Conclusions:
- A subset of neutrophils spontaneously expresses PR3 on their surface.
- Individual variability and long-term stability of PR3 surface expression on PMN exist.
- The presence of this PR3-expressing PMN subset may be significant in the pathogenesis of anti-PR3 ANCA-associated vasculitis.