טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentSchneider Yulia
SubjectThe Mechanism of Procalcitonin Secretion in Response
to Systemic Inflammatory Response Syndrome(SIRS)
DepartmentDepartment of Medicine
Supervisor Professor Oren Zinder


Abstract

Procalcitonin (PCT), was recently involved as a specific diagnostic marker of bacterial infection and sepsis. The aim of our study was to identify the specific patterns of PCT synthesis and release in response to bacterial infection or to sepsis-related triggers, such as lipopolysaccharide (LPS) and tumor necrosis factor-α (TNFα ).

Western blot analysis of plasma samples from the control as well as from the LPS or E.coli treated mice demonstrated two immunoreactive fragments of 13 kDa and 26kDa. LPS administration to mice led to an increase of the 26 kDa fragment, whereas treatment with E. coli preferentially increased 13 kDa fragment. Screening of different mice organs revealed a positive immunostaining only in spleen, specifically in the region of macrophage infiltration- marginal zone.

Among different cells types, monocytes and macrophages revealed higher levels of PCT in cell lysates. Macrophages incubated with LPS, TNFα  or with both, exhibited increased PCT levels in cell lysates. Moreover, cellular PCT levels were up-regulated following differentiation of monocytes to macrophages. In monocytes and macrophages cellular PCT was sinthezised in time dependent manner. Macrophages incubated with LPS, TNFα  or with both exhibited increased cellular PCT mRNA levels.

Thus, we demonstrate for the first time the possibility that PCT released to the serum in response to sepsis conditions, results from a dimerization of the protein. We have shown that monocytes and macrophages express PCT at the protein and mRNA levels, that are regulated by LPS and TNFa in an additive manner.