Neonatal murine macrophages show enhanced chemotactic capacity upon toll-like receptor stimulation
T Winterberg1, G Vieten, L Feldmann
1Pediatric Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany, winterberg.thomas@mh-hannover.de.
Background:
The neonatal surgical patient is threatened by exuberant inflammatory reactions. Neonatal macrophages are key players in this process. We investigated the ability of neonatal macrophages to initiate a local inflammatory reaction upon exposure to different bacterial or viral ligands to toll-like receptors (TLRs).
Methods:
Peritoneal wash outs from neonatal (<24 h) and adult (42 days) C57BL/6J mice were gained by peritoneal lavages. In a first set of experiments, macrophages were purified and stimulated for 6 h by four different TLR ligands. mRNA was extracted for transcriptome analysis. In a second set of experiments, lipopolysaccharide was applied into peritoneal cavities. After 6 h of incubation, the cellular composition of the inflamed cavities was evaluated by cytological staining as well as chipcytometry.
Results:
Neonatal murine peritoneal macrophages differed significantly in the expression of pro- and anti-chemotactic genes. Functional assignment of these genes revealed enhanced chemotactic potential of neonatal macrophages and was confirmed by a higher influx of pro-inflammatory cells into neonatal peritoneal cavities.
Conclusion:
Neonatal peritoneal macrophages demonstrated an enhanced chemotactic potential upon stimulation with four TLR ligands. This was associated with an increased influx of inflammatory cells to the peritoneal cavity. This might contribute to the strong inflammatory responses of neonates and preterms.
Insights
Neonatal macrophages show increased inflammatory cell attraction when exposed to toll-like receptor (TLR) ligands. This enhanced chemotactic potential in newborns may explain their heightened inflammatory responses.
Area of Science:
- Immunology
- Neonatal research
- Innate immunity
Background:
- Neonatal surgical patients are susceptible to severe inflammatory responses.
- Neonatal macrophages play a critical role in initiating these reactions.
- Understanding neonatal macrophage function is crucial for managing inflammatory conditions in newborns.
Purpose of the Study:
- To investigate the inflammatory response of neonatal macrophages upon stimulation with toll-like receptor (TLR) ligands.
- To compare the chemotactic potential of neonatal and adult macrophages.
- To elucidate the mechanisms underlying exaggerated neonatal inflammation.
Main Methods:
- Peritoneal macrophages were isolated from neonatal and adult C57BL/6J mice.
- Macrophages were stimulated with four different TLR ligands, followed by transcriptome analysis.
- Lipopolysaccharide (LPS) administration in vivo was used to assess cellular inflammatory responses via cytological staining and chipcytometry.
Main Results:
- Neonatal macrophages exhibited significant differences in pro- and anti-chemotactic gene expression compared to adult macrophages.
- Functional analysis revealed an enhanced chemotactic potential in neonatal macrophages.
- A higher influx of pro-inflammatory cells was observed in neonatal peritoneal cavities after stimulation.
Conclusions:
- Neonatal macrophages possess an enhanced chemotactic capacity when stimulated by TLR ligands.
- This enhanced potential correlates with increased inflammatory cell recruitment to the peritoneal cavity.
- These findings suggest a mechanism contributing to the heightened inflammatory responses seen in neonates and premature infants.
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