Timing of neutrophil tissue repopulation predicts restoration of innate immune protection in a murine bone marrow transplantation model.
It 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.
Cheretakis
Chrisovalantou
C
Canadian Institutes of Health Research Group in Matrix Dynamics, University of Toronto, Fitzgerald Bldg., 150 College Street, Rm 241, Toronto, Ontario Canada M5S 3E2.
Leung
Roland
R
Sun
Chun Xiang
CX
Dror
Yigal
Y
Glogauer
Michael
M
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007958:Leukocyte Count; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D009928:Organ Specificity; D018410:Pneumonia, Bacterial / Q000276:immunology; D011552:Pseudomonas Infections / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins