Serine pretease 억제제인 4-(2-aminoethyl) benzensulfonylfluoride (AEBSF)에 의한 호중구의 자연 세포사멸의 지연과 수지상 세포로의 전이분화 연구

Abstract

Neutrophils play a key role as a first line of defense and are known to acquire the characteristics of dendritic cells (DCs) under the appropriate conditions. The spontaneous apoptosis of neutrophils was delayed by treatment with 4-(2-aminoethyl) benzensulfonylfluoride (AEBSF), a serine protease inhibitor. AEBSF inhibited both caspase-3 and serine protease activities, whereas ZVAD-fmk, a pancaspase inhibitor, inhibited only caspase-3 activity. The life span of neutrophils was prolonged up to 5 days by AEBSF in the presence or absence of granulocyte macrophage colony stimulating factor(CM-CSF). DC surface markers, such as CD80, CD83, and MHC class ll were not expressed on neutrophils treated with AEBSF alone. CM-CSF failed to prolong the survival time of neutrophils up to3 days but increased the expression levels of DC markers on neutrophils in the presence of AEBSF. Expression levels of DC markers were the highest on neutrophils treated with CM-CSF and AEBSF for 3 days. AEBSF and CM-CSF-treated neutrophils stimulated proliferation of T cells in the presence of a superantigen, Staphylococcal enterotoxin B (SEB) but produced () in the absence of SEB. These results suggest that the inhibition of serine protease activity prolonged the life span of human neutrophils and combined treatment of neukophils with CM-CSF and serine protease inhibitor induced differentiation of neutrophils into DC-like cells.