Naslov
The Role of Granzyme K in Inflammatory Response

Autori
L.D. Fast, M. Ručević, G. Jay, Y.P. Lim.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Journal of Immunology / - Bethesda (MD), 2006

Skup
The Annual Meeting of The American Association of Immunologists (AAI

Mjesto i datum
Boston (MA), Sjedinjene Američke Države, 12.05.2006. - 16.05.2006

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
Granzym K; serine protease; cytotoxic cells; sepsis; diagnostic marker

Sažetak
Granzyme K is one of a family of serine proteases found in the granules of murine and human NK cells and cytolytic T lymphocytes (CTL). We had observed that decreased levels of inter- -inhibitor proteins, the putative inhibitor of granzyme K, correlated with increased mortality in sepsis. This led us to hypothesize that uninhibited granzyme K could contribute to the severity of sepsis. As a first step to investigate a possible role of granzyme K in sepsis, a competitive ELISA was developed to measure granzyme K levels in biological fluids. The plasma levels of granzyme K were measured in samples obtained from normal controls, patients admitted to the emergency department with a putative diagnosis of sepsis or from patients enrolled in a clinical trial for severe sepsis. The results indicated that there were significantly increased levels of granzyme K in the patients from the emergency department and significantly decreased levels of granzyme K in the clinical trial patients. The basis for the differences in these patient populations has not been determined. Because the 2 patient populations had similar APACHE II scores, one possible explanation for the difference is that the patients admitted to the emergency room where at a earlier stage of sepsis than the clinical trial patients. This would suggest that granzyme K levels would increase and then decrease as has been observed with cytokine levels in response to inflammatory stimuli. As one approach to measure the changes in granzyme K levels in response to inflammatory stimuli, C57BL/6 recipients were injected with 25 ug LPS and the plasma levels of granzyme K measured at various timepoints after LPS injection. The results indicated that there was a increase in granzyme K levels that peaked at 48 hours in these recipients. These increases in granzyme K levels occurred much later than the dramatic increases in cytokine levels (0 – 12 hours) This could provide one explanation for why increased levels of granzyme K could be detected in patients being admitted to the emergency room followed by decreased levels of granzyme K in patients that had progressed further in the septic response. These findings suggest that measuring the levels of granzyme K could be a useful diagnostic marker for sepsis.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Kliničke medicinske znanosti, Biotehnologija

POVEZANOST RADA