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Neutrophil migration into the peritoneum is P-selectin dependent, but sequestration in lungs is selectin independent
D J Wickel1, M Mercer-Jones, J C Peyton
1Department of Surgery, University of Louisville School of Medicine and the Veterans Affairs Medical Center, Kentucky 40292, USA.
Abstract:
Neutrophil (PMN) influx into the peritoneal cavity in response to bacterial peritonitis is an indispensable aspect of host defense. PMNs also are responsible for the remote organ injury observed after major abdominal infection. The aim of this study was to examine the effect of selectin blockade on PMN migration into the peritoneum and on PMN sequestration in the lungs, early in the course of peritonitis. Cecal ligation and puncture (CLP) was performed on P-selectin-deficient (P-def) mice and their genetic controls (C57). Both groups were treated with anti-E-selectin antibody, anti-L-selectin, or isotypic control immunoglobulin G at the time of CLP. 6 h after CLP, mice were sacrificed. Peritoneal PMN migration decreased in P-def mice compared with C57 controls after CLP. Blockade of E- or L-selectin alone in controls did not alter peritoneal PMN influx or circulating PMNs after CLP. In the P-def mice, treatment with anti-E-antibody or anti-L-antibody nearly eliminated PMN influx into the peritoneum. In contrast, circulating PMNs markedly increased after CLP in P-def mice when compared with baseline values. Lung myeloperoxidase increased in all groups of mice following CLP. Blockade of P-selectin with anti-P-selectin antibody elicited a response similar to that observed in the P-def mice. In conclusion, P-selectin mediates PMN influx into the peritoneal cavity, while E- and L-selectins do not appear to play any significant role in the 6 h time period following CLP. Lung PMN sequestration, after CLP, occurred independent of P-, E-, or L-selectin expression. Blockade of P-selectin during peritonitis appears to be potentially deleterious by preventing early PMN influx into the compartment containing the septic focus.
Insights
P-selectin blockade prevents early neutrophil migration into the peritoneum during bacterial peritonitis, potentially harming host defense. E- and L-selectins do not significantly impact this early migration or lung sequestration.
Area of Science:
- Immunology
- Cell Biology
- Sepsis Research
Background:
- Neutrophil (PMN) migration is crucial for host defense against bacterial peritonitis but also contributes to remote organ injury.
- Understanding the role of selectins in PMN migration during peritonitis is key to developing targeted therapies.
Purpose of the Study:
- To investigate the impact of P-, E-, and L-selectin blockade on PMN migration into the peritoneal cavity.
- To assess the effect of selectin blockade on PMN sequestration in the lungs during early peritonitis.
Main Methods:
- Cecal ligation and puncture (CLP) model in P-selectin-deficient (P-def) mice and wild-type controls.
- Administration of anti-E-selectin, anti-L-selectin, or control immunoglobulin G antibodies.
- Analysis of peritoneal PMN influx and lung myeloperoxidase activity 6 hours post-CLP.
Main Results:
- P-selectin deficiency significantly reduced peritoneal PMN influx post-CLP.
- Blockade of E- or L-selectin alone did not alter peritoneal PMN migration.
- In P-def mice, anti-E- or anti-L-selectin treatment nearly abolished peritoneal PMN influx, increasing circulating PMNs.
- Lung PMN sequestration occurred independently of P-, E-, or L-selectin expression.
Conclusions:
- P-selectin is the primary mediator of early PMN influx into the peritoneum during CLP-induced peritonitis.
- E- and L-selectins play a minor role in this early peritoneal PMN migration.
- P-selectin blockade may be detrimental by hindering the initial inflammatory response at the infection site.