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Modulation of the Granzyme B Inhibitor Proteinase Inhibitor 9 (PI-9) by Activation of Lymphocytes and Monocytes in Vitro and by Epstein-Barr Virus and Bacterial Infection

C F Classen, P I Bird, K-M Debatin

Clin Exp Immunol. 2006 Mar;143(3):534-42.

PMID: 16487253

Abstract:

Proteinase inhibitor 9 (PI-9) is an intracellular serpin expressed in lymphocytes and monocyte-derived cells. It is the only known endogenous natural antagonist of granzyme B (GrB), and its proposed function is protection of cells from misdirected GrB. We have studied the regulation of PI-9 in primary peripheral blood mononuclear cells (PBMCs) following ex-vivo stimulation, and in PBMCs from patients suffering from viral or bacterial infections. By intracellular flow cytometry, we found identical PI-9 expression in all lymphocyte subsets, lower levels in monocytes and none in granulocytes. PI-9 was stable for 48 h in the presence of cycloheximide, indicating slow protein turnover. Incubation of PBMCs with several stimuli including lipopolysaccharide (LPS) led to up-regulation in the monocyte, but not the lymphocyte fraction, within 48 h, inhibitable by the NF-kappaB inhibitor pyrrolidin dithiocarbamate (PTDC). Up-regulation of PI-9 was observed in lymphocytes and monocytes of patients with acute Epstein-Barr virus (EBV), but not bacterial infection. Preterm infants had similar PI-9 expression as adults in monocytes, but lower in lymphocytes, decreasing during bacterial infection. Taken together, our data indicate that PI-9 is rapidly up-regulated upon stimulation of monocytes, but not lymphocytes. By protecting monocytes and macrophages from misdirected GrB in the inflammatory process, PI-9 might be involved in the regulation of antigen presentation.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP1622426134 Serine Hydrolase Inhibitor-9 Serine Hydrolase Inhibitor-9 1622426-13-4 Price
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