Macrophages in Spleen and Liver Direct the Migration Pattern of Rat Neutrophils During Inflammation

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.