Mouse bone marrow contains large numbers of functionally competent neutrophils

J Leukoc Biol. 2004 Apr;75(4):604-11. doi: 10.1189/jlb.0703340. Epub 2003 Dec 23.

Abstract

The mouse has become an important model for immunological studies including innate immunity. Creating transgenic mice offers unique possibilities to study gene-function relationships. However, relatively little is known about the physiology of neutrophils from wild-type mice. Do they behave like human neutrophils, or are there species-specific differences that need to be considered when extrapolating results from mice to humans? How do we isolate neutrophils from mice? For practical reasons, many studies on mouse neutrophils are done with bone marrow cells. However, human bone marrow neutrophils appear to be heterogeneous and functionally immature. We have isolated and compared neutrophils from mouse bone marrow and from peripheral blood obtained by tail bleeding. Using the same Percoll density gradient for both preparations, we have obtained morphologically mature neutrophils from bone marrow and blood. Both cell populations responded to formylmethionyl-leucyl-phenylalanine (fMLF) with primary and secondary granule release and superoxide production. Quantitative analysis of our data revealed minor differences between cells from bone marrow and blood. Superoxide production and primary granule release were stimulated at lower fMLF concentrations in blood neutrophils. However, the amplitude and the kinetics of maximal responses were similar. The principal difference was the lifespan of the two cell populations. Bone marrow cells survived significantly longer in culture, which may suggest that they are receiving antiapoptic signals that are absent in the blood. Our data suggest that mice have a large reservoir of functionally competent neutrophils in their bone marrow. This reservoir may be needed to replace circulating neutrophils rapidly during infection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Cells / cytology*
  • Blood Cells / drug effects
  • Blood Cells / metabolism
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cell Count
  • Cell Separation / methods
  • Cell Survival / physiology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Glucuronidase / metabolism
  • Humans
  • Lactoferrin / metabolism
  • Mice
  • Mice, Inbred C57BL
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / cytology*
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Secretory Vesicles / drug effects
  • Superoxides / metabolism

Substances

  • Superoxides
  • N-Formylmethionine Leucyl-Phenylalanine
  • Glucuronidase
  • Lactoferrin