Dynamic changes in neutrophil defensins during endotoxemia
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M E Klut1, B A Whalen, J C Hogg
1University of British Columbia McDonald Research Laboratories, iCAPTURE Centre, St. Paul's Hospital, Vancouver, British Columbia, Canada. Mklut@mrl.ubc.ca
Abstract:
Bacterial endotoxin or lipopolysaccharide (LPS) is an important causative agent of sepsis. This study determines the expression of defensins NP-2 and NP-5 and the function of polymorphonuclear leukocytes (PMN) in rabbits treated with LPS. PMN functional activity was assessed by measuring CD18 expression and H(2)O(2) production and by examining the lungs. NP-2 and, to a minor extent, NP-5 of circulating PMN increase during endotoxemia. This early increase is concomitant with neutrophilia and elevated CD18 expression and H(2)O(2) production, as well as with enhanced NP-2 immunoreactivity in pulmonary microvessels. A decline in defensins, shortly after the last LPS treatment, is associated with a decrease in the circulating activated PMN and enhanced immunoreactivity in the inflammatory cells, as well as with lung tissue damage. This study shows that LPS-induced changes in the defensins of circulating PMN correlate with the number and activated condition of these cells and suggests that PMN-derived products implement the inflammatory reaction that leads to lung injury and sepsis.
Insights
Bacterial endotoxin (LPS) increases defensins in circulating immune cells during sepsis. These changes correlate with immune cell activation and lung injury, suggesting a role in sepsis progression.
Area of Science:
- Immunology
- Microbiology
- Pathology
Background:
- Bacterial endotoxin (lipopolysaccharide, LPS) is a key factor in sepsis development.
- Defensins are antimicrobial peptides with roles in innate immunity.
- Polymorphonuclear leukocytes (PMNs) are crucial immune cells involved in sepsis pathogenesis.
Purpose of the Study:
- To investigate the expression of defensins NP-2 and NP-5 in PMNs during LPS-induced endotoxemia in rabbits.
- To assess the functional activity of PMNs, including CD18 expression and hydrogen peroxide (H2O2) production.
- To correlate PMN defensin levels and function with lung injury in a sepsis model.
Main Methods:
- Rabbits were treated with LPS to induce endotoxemia.
- Expression of NP-2 and NP-5 defensins in circulating PMNs was measured.
- PMN functional activity was assessed via CD18 expression and H2O2 production.
- Pulmonary microvessel and lung tissue were examined for defensin immunoreactivity and damage.
Main Results:
- Circulating PMNs showed increased NP-2 and, to a lesser extent, NP-5 expression during endotoxemia.
- This increase coincided with neutrophilia, elevated CD18 expression, and H2O2 production.
- A subsequent decline in defensins correlated with reduced circulating activated PMNs and increased lung tissue damage.
Conclusions:
- LPS-induced changes in PMN defensins (NP-2, NP-5) reflect the number and activation state of these cells.
- PMN-derived products, influenced by defensin levels, appear to mediate the inflammatory response leading to sepsis-associated lung injury.
- Defensins may play a significant role in the pathogenesis of sepsis and endotoxemia.
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