Abstract
AbstractIt has been suggested that neutrophil tissue repopulation following bone marrow transplantation (BMT) serves as an earlier and more relevant marker of susceptibility to infection than circulating neutrophil counts. In a previous study using an oral rinse protocol, we found that oral neutrophil recovery always preceded blood neutrophil engraftment and that the day of oral neutrophil detection served as a predictor of patient susceptibility to infection after BMT. Consequently, we have developed and validated a mouse BMT model which uses bone marrow transplants containing enhanced green fluorescent protein-expressing neutrophils to follow neutrophil tissue repopulation after BMT. Using this in vivo cell migration model, we assessed the significance of neutrophil tissue recruitment kinetics with neutrophil functionality and in vivo bacterial killing after BMT. Using the animal model, we have demonstrated that protection against bacterial infection is conferred at the time of neutrophil tissue delivery, which always occurs before neutrophils are detected in the blood. We therefore conclude that neutrophil tissue recovery is an early measure of the restoration of cellular innate immune function after BMT. This model will help us better understand the factors regulating neutrophil recruitment to the tissues.
Highlights
Introduction we have developed and validated a mouse bone marrow transplantation (BMT) model which uses bone marrow transplants containing enhanced green fluorescent protein–expressing neutrophils to follow neutrophil tissue repopulation after BMT
Myeloid engraftment should mark the beginning of hematologic recovery and resolution of neutropenia, some bone marrow transplantation (BMT) patients who have obtained absolute neutrophil count (ANC) that suggest engraftment continue to experience life-threatening, prolonged, or recurrent infection, whereas others who present with an ANC less than 0.5 ϫ 109/L do not develop any fever related to infection.[2]
Recipient mice were reconstituted by intravenous tail vein injection with 3 to 6 ϫ 106 bone marrow cells collected from mice with E-GFP–expressing granulocytes.[8,9,10]
Summary
Introduction we have developed and validated a mouse BMT model which uses bone marrow transplants containing enhanced green fluorescent protein–expressing neutrophils to follow neutrophil tissue repopulation after BMT. Given the obvious difficulties in studying neutrophil dynamics in human patients in vivo, animal models have been extensively used as experimental model systems Most of those studies have focused primarily on circulating neutrophil kinetics and overall neutrophil production.[5,6] Our goal was to develop a murine BMT model system that would allow us to determine whether the timing of neutrophil tissue repopulation following transplantation is a better predictor of innate immune function recovery than the timing of neutrophil reappearance in the blood. We demonstrate here the importance of early neutrophil tissue repopulation after BMT in conferring protection from bacterial infection
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