Premium
Altered caspase expression results in delayed neutrophil apoptosis in acute pancreatitis
Author(s) -
O’Neill Sean,
O’Neill Amanda J.,
Conroy Eimear,
Brady Hugh R.,
Fitzpatrick John. M.,
Watson R. William G.
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.68.1.15
Subject(s) - apoptosis , biology , propidium iodide , neutrophil extracellular traps , immunology , inflammation , flow cytometry , programmed cell death , biochemistry
Acute pancreatitis (AP) may lead to the development of multiple organ dysfunction syndrome (MODS), especially in severe cases. Resolution of such inflammatory responses is dependent on neutrophil apoptosis. Delays in this apoptotic response are associated with persistent inflammation and subsequent tissue damage. The aim of this study is to determine the effects of AP on neutrophil apoptosis and to investigate the underlying mechanisms involved. Neutrophils and serum were isolated from control ( n =10) and from patients with AP (mild, n =35, and severe, n =5). Neutrophil apoptosis was assessed by propidium iodide DNA staining using flow cytometry. Caspase, glutathione‐S‐transferase (GST), and Mcl‐1 protein expression were assessed by SDS‐PAGE western blotting. Serum interleukin (IL)‐1β and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) levels were measured by ELISA. Neutrophils isolated from patients with AP show a significant delay in spontaneous neutrophil apoptosis. Serum factors contributed to this delay with increases in IL‐1β and GM‐CSF. Isolated neutrophils were resistant to Fas antibody‐induced apoptosis. Caspases represent a central mechanism for spontaneous and Fas antibody‐induced neutrophil apoptosis. Procaspase 3 expression was decreased in mild and severe cases, but this effect was independent of serum factors. Increases in GST expression may also contribute to the antiapoptotic effect. Altered caspase expression may represent an additional factor contributing to delayed neutrophil apoptosis. This may contribute to the development of AP and its related complications.