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Macrophages in spleen and liver direct the migration pattern of rat neutrophils during inflammation
E Knudsen1, H B Benestad, T Seierstad
1Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. eirunn.knudsen@basalmed.uio.no
Objective:
The exact fate of polymorphonuclear neutrophilic granulocytes (PMN; neutrophils) after their mobilization from the bone marrow is not known. It is believed that they, after a relatively short lifespan (1-3 d), become apoptotic and phagocytosed by macrophages. We have recently shown that transfused neutrophils sequestrate not only in lungs, liver and spleen, but also to a large extent in the bone marrow, possibly because of uptake by macrophages. Hence, we studied if inactivation of macrophages would alter the pattern of neutrophil migration.
Methods:
We used transfused congenic or syngeneic neutrophils in rats with or without sterile peritonitis, induced by a casein preparation (Bacto-Tryptone). To perturb macrophage function, we either killed them with liposome-encapsulated clodronate or overloaded them with inert phagocytosable particles. Transfused neutrophils were tracked with flow cytometric or radiometric methods.
Results:
Not more than a small portion of the neutrophils migrated to the inflamed peritoneal cavity under any circumstance. Their ecotaxis to liver and spleen was reduced in rats with liver and spleen macrophages either congested with polystyrene particles or depleted by clodronate. The bone marrow uptake and blood retention of transfused neutrophils were increased in macrophage-depleted rats 18 h after transfusion. In rats depleted of liver macrophages only, the sequestration in the liver was reduced, without detectably changed uptake in bone marrow and spleen.
Conclusion:
Macrophages are instrumental to the neutrophil migration stream in the organism, and their function in this regard is robust and not easily decreased by inert phagocytosable particles or a killing agent.
Insights
Macrophages play a crucial role in directing neutrophil migration. Studies show that disrupting macrophage function significantly alters neutrophil distribution, increasing bone marrow uptake and blood retention.
Area of Science:
- Immunology
- Hematology
Background:
- The fate of polymorphonuclear neutrophilic granulocytes (neutrophils) post-mobilization remains unclear.
- Neutrophils are believed to undergo apoptosis and phagocytosis by macrophages after a short lifespan.
- Previous research indicated neutrophil sequestration in various organs, including bone marrow, potentially due to macrophage uptake.
Purpose of the Study:
- To investigate the influence of macrophage inactivation on neutrophil migration patterns.
- To understand the role of macrophages in the distribution of circulating neutrophils.
Main Methods:
- Utilized transfused congenic or syngeneic neutrophils in rats.
- Induced sterile peritonitis using casein preparation.
- Perturbed macrophage function via clodronate-induced depletion or particle overload.
- Tracked neutrophil migration using flow cytometry and radiometric methods.
Main Results:
- Reduced neutrophil migration to inflamed peritoneal cavities regardless of experimental conditions.
- Decreased neutrophil ecotaxis to liver and spleen when macrophages were depleted or congested.
- Increased bone marrow uptake and blood retention of neutrophils in macrophage-depleted rats.
- Selective liver macrophage depletion reduced liver sequestration without affecting bone marrow or spleen uptake.
Conclusions:
- Macrophages are essential regulators of neutrophil migration within the body.
- Macrophage function in neutrophil trafficking is robust and not easily impaired by inert particles or depletion agents.
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