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Updated: Aug 19, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Elimination of various subpopulations of macrophages and the development of multiple-organ dysfunction syndrome in
G A Nieuwenhuijzen1, M F Knapen, T Hendriks
1Department of Surgery, Academic Hospital Nijmegen, The Netherlands.
Objective:
To evaluate the role of specific macrophage subpopulations in the development of zymosan-induced multiple-organ dysfunction syndrome by selective elimination of liver, splenic, alveolar, and peritoneal macrophages.
Design:
Randomized animal trial.
Setting:
Central animal laboratory at the University Hospital Nijmegen, Nijmegen, the Netherlands.
Animals:
Male C57Bl/6 mice.
Interventions:
Elimination of macrophages was accomplished by administration of multilamellar liposomes that contained dichloromethylene bisphosphonate (Cl2MBP). Intravenous, intratracheal, and intraperitoneal administrations induced an elimination of liver and splenic, alveolar, and peritoneal and omental macrophages, respectively. Zymosan (1 mg/g) was injected intraperitoneally at day 0. The liposomes that contained Cl2MBP were administered before and after zymosan challenge. At day 12, all surviving mice were killed.
Main Outcome Measures:
The body weights, temperatures, and mortality rates of the mice were monitored daily. Relative organ weights (ROWs) were calculated from the lungs, liver, spleen, and kidneys after the mice were killed.
Results:
The liposomes that contained Cl2MBP, administered intravenously before or after zymosan challenge, did not induce significant changes in the body weight, temperature, or mortality rate. The ROW of the liver was significantly decreased in both treatment groups. Elimination of liver and splenic macrophages after zymosan challenge induced an increased ROW of the lung and a decreased ROW of the liver. The liposomes that contained Cl2MBP, administered intratracheally before zymosan challenge, completely prevented deaths. The body weights, temperatures, and ROWs of the mice were not changed. The liposomes that contained Cl2MBP, administered intraperitoneally, did not change the body weight, temperature, or ROW. The liposomes that contained Cl2MBP, administered intraperitoneally before zymosan challenge, increased the mortality from 50% to 90%.
Conclusions:
These data show that the elimination of specific macrophage subpopulations and the elimination on specific time points in this model had differential effects, indicating a differential role of specific macrophage subpopulations, either protective or detrimental, in the development of multiple-organ dysfunction syndrome.
Insights
Selective elimination of macrophages reveals their differential roles in multiple-organ dysfunction syndrome. Targeting specific macrophage subpopulations at precise times can be protective or detrimental, offering insights into managing this condition.
Area of Science:
- Immunology
- Pathophysiology
- Inflammation
Background:
- Macrophage heterogeneity plays a crucial role in immune responses.
- Understanding the specific functions of macrophage subpopulations is vital for developing targeted therapies.
- Multiple-organ dysfunction syndrome (MODS) is a complex condition with significant mortality.
Purpose of the Study:
- To investigate the distinct roles of liver, splenic, alveolar, and peritoneal macrophages in zymosan-induced multiple-organ dysfunction syndrome (MODS).
- To evaluate the effects of selective macrophage depletion at different time points on MODS development.
Main Methods:
- A randomized animal trial was conducted using male C57Bl/6 mice.
- Macrophage subpopulations were selectively eliminated using liposomes containing dichloromethylene bisphosphonate (Cl2MBP) administered via intravenous, intratracheal, or intraperitoneal routes.
- Zymosan was administered to induce MODS, with liposomes given before and after the challenge.
- Mice were monitored for body weight, temperature, mortality, and relative organ weights.
Main Results:
- Intravenous administration of Cl2MBP-liposomes did not significantly alter body weight, temperature, or mortality but decreased liver relative organ weight.
- Elimination of liver and splenic macrophages post-zymosan challenge led to increased lung and decreased liver relative organ weights.
- Intratracheal administration of Cl2MBP-liposomes before zymosan challenge completely prevented mortality without affecting other parameters.
- Intraperitoneal administration of Cl2MBP-liposomes before zymosan challenge increased mortality from 50% to 90%.
Conclusions:
- The elimination of specific macrophage subpopulations at distinct time points exerts differential effects in the zymosan-induced MODS model.
- These findings highlight the context-dependent, either protective or detrimental, roles of specific macrophage subpopulations in the pathogenesis of MODS.
