Proteinase 3 Expression on Neutrophil Membranes from Patients with Infectious Disease

Abstract number: P2371

Matsumoto¹ T, Kaneko² T, Wada³ H, Kobayashi¹ T, Abe⁴ Y, Nobori³ T, Shiku¹ H, Stearns-Kurosawa⁵ DJ, Kurosawa⁵ S

¹¹The Second Department of Internal Medicine, Mie University School of Medicine, Tsu City, Japan ¹¹The Second Department of Internal Medicine, Mie University School of Medicine, Tsu City, Japan ²²Patient Safety Division, Mie University Hospital, Tsu City, Japan ³³Department of Laboratory Medicine, Mie University School of Medicine, Tsu City, Japan ⁴⁴Laboratory Division, Mie University Hospital, Tsu City, Japan ⁵⁵Free Radical Biology & Aging, Oklahoma Medical Research Foundation, Oklahoma City, USA

Proteinase-3 (PR3) is an abundant serine proteinase stored in neutrophils and released to the cell surface upon activation. Neutrophil membrane PR3 (mPR3) expression is typically bimodal and the sub-population of neutrophils with high expression (PR3-high) or low expression (PR3-low) varies among individuals, but is extremely stable for each individual over prolonged time periods. We examined mPR3 expression on purified neutrophils from patients with infectious diseases and from healthy volunteers (controls) by flow cytometry, with and without in vitro stimulation by TNF-alpha and N-formyl-L-methionyl-L-phenylalanine. We confirmed high variability in the percentage of PR3-high (%PR3-high) neutrophils both from controls (n= 64) and patients (n= 56). The%PR3-high was significantly greater from the patients than controls (72 ± 19% vs 55 ± 20%, P < 0.0001). Over time, some cases showed a significant increase in the %PR3-high sub-population. These patients eventually died from sepsis and the changes in neutrophil PR3 expression may be related to the inflammation severity. The level of PR3 antigen expression and its distribution in the PR3-high sub-population in resting and activated neutrophils from patients was significantly higher than in healthy controls (P < 0.001, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r= 0.465, n= 56, P < 0.001). mPR3 expression and distribution in neutrophils activated in vitro also correlated with CRP levels (r= 0.442, n= 56, P < 0.001). mPR3 and %PR3 of resting or activated neutrophils were significantly higher in patients with SIRS (n= 14) than non-SIRS (n= 42), respectively (P < 0.001, P < 0.001). The data indicate that membrane expression of PR3 on neutrophils is greatly influenced by an in vivo inflammatory environment.