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Expression of adhesion molecules on circulating PMN during hyperdynamic endotoxemia
1Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Abstract:
In a porcine model of hyperdynamic endotoxemia, we studied the numerical expression of L-selectin and beta 2-integrins on circulating polymorphonuclear leukocytes (PMN). Functional changes of beta 2-integrins were determined by the adhesion of PMN to C3-coated zymosan particles. Anesthesized pigs received a continuous infusion of Salmonella abortus-equi endotoxin (5 micrograms.kg body wt-1.h-1) for 270 min (endotoxin group; n = 7). A control group received 0.9% NaCl (n = 6). L-selectin had decreased 30 min after the induction of endotoxemia [59.1 +/- 11.9 vs. 91.6 +/- 15.5 relative fluorescence units (RFU) at baseline; P < 0.05], reaching minimal values after 150 min (23.9 +/- 3.9 RFU in endotoxin group vs. 95.2 +/- 30.4 RFU in control group; P < 0.05). PMN adhesion to C3-coated zymosan increased at 30 min (41.3 +/- 9.9% in endotoxin group vs. 2.4 +/- 1.1% in control group; P < 0.05) and remained significantly elevated thereafter. In contrast to the rapid shedding of L-selectin and functional upregulation of beta 2-integrins, the numerical expression of beta 2-integrins remained unchanged until 60 min (44.8 +/- 2.8 vs. 32.2 +/- 1.7 RFU at baseline; P < 0.05); compared with the control group, significantly elevated values were observed 150 min after the start of endotoxin (48.9 +/- 2.4 RFU in endotoxin group vs. 36.5 +/- 2.7 RFU in control group; P < 0.05). We conclude that numerical and functional expressions of beta 2-integrins are dissociated during endotoxemia. Although upregulation of beta 2-integrins might render PMN more adhesive to the vascular endothelium, the presence of activated PMN in the circulation suggests that low expression of L-selectin might impede adhesion.
Insights
Endotoxemia rapidly decreases L-selectin on polymorphonuclear leukocytes (PMN) while increasing their adhesion. Beta 2-integrin expression and function are dissociated, suggesting L-selectin shedding impedes PMN adhesion during endotoxemia.
Area of Science:
- Immunology
- Cell Biology
- Physiology
Background:
- Endotoxemia involves complex inflammatory responses affecting leukocyte function.
- Polymorphonuclear leukocytes (PMN) play a critical role in the inflammatory cascade.
- L-selectin and beta 2-integrins are key adhesion molecules on PMN.
Purpose of the Study:
- To investigate the expression and function of L-selectin and beta 2-integrins on PMN during hyperdynamic endotoxemia in a porcine model.
- To determine the relationship between numerical expression and functional activity of beta 2-integrins.
Main Methods:
- A porcine model of hyperdynamic endotoxemia induced by Salmonella abortus-equi endotoxin infusion.
- Quantification of L-selectin and beta 2-integrin expression on circulating PMN using flow cytometry.
- Assessment of PMN functional activation via adhesion to C3-coated zymosan particles.
Main Results:
- Endotoxemia caused a rapid decrease in L-selectin expression on PMN.
- PMN adhesion to C3-coated zymosan particles significantly increased, indicating functional upregulation of beta 2-integrins.
- Numerical expression of beta 2-integrins remained unchanged initially but increased later in endotoxemia.
- A dissociation was observed between the numerical and functional expression of beta 2-integrins.
Conclusions:
- The study demonstrates a dissociation between the numerical and functional expression of beta 2-integrins during endotoxemia.
- Rapid L-selectin shedding and functional beta 2-integrin upregulation may contribute to PMN activation and altered adhesion.
- Low L-selectin expression might hinder PMN adhesion despite beta 2-integrin activation.