Endotoxin inhibits apoptosis but induces primary necrosis in neutrophils.
Lipopolysaccharide (LPS) is known to prolong the functional lifespan of neutrophils at a site of infection by preventing apoptosis through inhibitor of apoptosis proteins (IAPs). We hypothesized that the increased neutrophil lifespan ultimately leads to a larger fraction of cells undergoing uncontrolled, primary necrosis. Diluted venous whole blood was incubated with increasing concentrations of LPS for up to 36 hr. The percentages of apoptotic, necrotic and viable neutrophils were assessed using the Annexin V/propidium iodide flow cytometric assay. LPS led to a reduction of neutrophil apoptosis and increased the number of viable cells at 12, 24, and 36 hr of incubation. At the same time intervals, there was a significant increase in the percentage of cells undergoing primary necrosis for all concentrations of LPS (e.g., 10 ng/ml LPS at 24 h produced a mean increase from 9.6% in controls to 30.6%, p < 0.001). This increase in direct neutrophil necrosis following LPS activation may amplify local proinflammatory effects through less well controlled release of neutrophil contents into surrounding tissue.
Turina
Matthias
M
Department of Surgery, The Price Institute of Surgical Research, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA. m0turi01@gwise.louisville.edu
Miller
Frederick N
FN
McHugh
Patrick P
PP
Cheadle
William G
WG
Polk
Hiram C
HC
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009336:Necrosis / Q000139:chemically induced*; D009504:Neutrophils / Q000473:pathology*; D013997:Time Factors
D017304:Annexin A5; D008070:Lipopolysaccharides