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Kinetic evaluation of the pool sizes and proliferative response of neutrophils in bacterially challenged aging mice
G Rothstein1, R D Christensen, B R Nielsen
1Department of Medicine, University of Utah School of Medicine, Salt Lake City 84132.
Abstract:
Clinical observations during infection suggest that in aged patients, the kinetic or proliferative responses of neutrophils to infection may be deranged. To test this hypothesis, the neutrophil responses of 6-month-old and 30-month-old mice were compared. After intrapulmonary injection of Escherichia coli, young mice exhibited neutrophilia and diminution of the neutrophil storage pool (NSP) by a mean of 6.4 x 10(6) neutrophils/two femurs. This was accompanied by an increase in the pool of CFU-GM from a control value of 1.1 x 10(5) cells/two femurs (range 0.7 to 1.4) to 1.5 x 10(5) (1.1 to 1.9) (P less than .05) and the thymidine suicide (relative proliferative rate) of CFU-GM rose from 27% (19 to 42) to 51% (31 to 61) (P less than .05). Furthermore, the CFU-GM of infected young mice displayed enhanced differentiation to the neutrophil series. In contrast, old mice exhibited a greater mean diminution of the NSP: 12.8 x 10(6) neutrophils. Also, old mice experienced a reduction in CFU-GM from 2.3 x 10(5) (1.0 to 3.9) (controls) to 1.3 x 10(5) (1.2 to 1.5)/two femurs (P less than .05), a reduction in the proliferation of CFU-GM and reduced differentiation of CFU-GM to neutrophils. These experiments establish that the neutrophil response of infected old mice is disordered, with exaggerated depletion of the NSP and lack of stimulus-driven granulocytopoiesis as reflected by a paradoxical reduction in the number and proliferative rate of precursors. This defect may be compounded by decreased differentiation of precursors to neutrophils.
Insights
Aging impairs neutrophil responses to infection. Older mice show exaggerated depletion of neutrophil storage pools and reduced precursor cell proliferation and differentiation, unlike younger mice with robust responses.
Area of Science:
- Immunology
- Gerontology
- Hematopoiesis
Background:
- Clinical observations suggest aged individuals have altered neutrophil responses to infection.
- Neutrophils are critical immune cells for combating bacterial infections.
- Age-related changes in immune cell kinetics and proliferation are not fully understood.
Purpose of the Study:
- To investigate age-related differences in neutrophil kinetic and proliferative responses to infection.
- To compare neutrophil responses in young versus aged mice following bacterial challenge.
Main Methods:
- Intrapulmonary infection with Escherichia coli in young (6-month-old) and aged (30-month-old) mice.
- Quantification of neutrophil storage pool (NSP) depletion.
- Analysis of colony-forming unit-granulocyte-macrophage (CFU-GM) number, proliferation (thymidine suicide), and differentiation.
Main Results:
- Young mice exhibited neutrophilia, NSP depletion, increased CFU-GM, and enhanced CFU-GM proliferation and differentiation.
- Aged mice showed significantly greater NSP depletion.
- Aged mice displayed reduced CFU-GM numbers, proliferation, and impaired differentiation to neutrophils.
Conclusions:
- Aging disrupts neutrophil responses to infection, characterized by exaggerated NSP depletion.
- Aged mice exhibit a lack of stimulus-driven granulocytopoiesis, with reduced precursor cell numbers and proliferation.
- Impaired differentiation of neutrophil precursors may further compromise immune defense in aged individuals.