mRNA and Protein Expression Levels of Secretory Leukocyte Protease Inhibitor (SLPI) are Severely Reduced in Patients with Severe Congenital Neutropenia (CN)

Secretory Leukocyte Protease Inhibitor (SLPI) is a cationic serine protease inhibitor with antiprotease, primarily anti-NeutrophilELastase (NE), activities. The molecular interaction and the balance between NE and SLPI is tightly regulated. We identified severe diminished levels of SLPI mRNA in myeloid cells and in plasma of severe congenital neutropeniapatients (CN), as compared to cyclic neutropeniapatients (CyN) and to healthy individuals. We further analysed whether diminished levels of SLPI could cause “maturation arrest“ of myeloid cells seen in CN patients. We inhibited SLPI in the myeloid cell line NB4 and in hematopoietic CD34 + cells with SLPI-specific shRNA and analysed ATRA- or G-CSF-triggered myeloid differentiation, respectively. Indeed, myeloid differentiation was diminished in NB4 cells and in CD34 + cells transduced with SLPI-specific shRNA, as compared to control shRNAtransduced cells. which was accompanied by G 0 /G 1 cell cycle arrest of SLPI shRNAtransduced cells. The mechanisms of “maturation arrest” of granulopoiesis due to SLPI inhibition remain to be investigated.