Sympathetic Denervation Alters the Inflammatory Response of Resident Muscularis Macrophages upon Surgical Trauma and Ameliorates Postoperative Ileus in Mice.
Shilpashree MalleshReiner SchneiderBianca SchneikerMariola LyssonPatrik EfferzEugene LinWouter J de JongeSven WehnerPublished in: International journal of molecular sciences (2021)
Interactions between the peripheral nervous system and resident macrophages (MMs) modulate intestinal homeostatic functions. Activation of β2-adrenergic receptors on MMs has been shown to reduce bacterial challenges. These MMs are also crucial for the development of bowel inflammation in postoperative ileus (POI), an iatrogenic, noninfectious inflammation-based motility disorder. However, the role of the sympathetic nervous system (SNS) in the immune modulation of these MMs during POI or other noninfectious diseases is largely unknown. By employing 6-OHDA-induced denervation, we investigated the changes in the muscularis externa by RNA-seq, quantitative PCR, and flow cytometry. Further, we performed transcriptional phenotyping of sorted CX3CR1+ MMs and ex vivo LPS/M-CSF stimulation on these MMs. By combining denervation with a mouse POI model, we explored distinct changes on CX3CR1+ MMs as well as in the muscularis externa and their functional outcome during POI. Our results identify SNS as an important mediator in noninfectious postoperative inflammation. Upon denervation, MMs anti-inflammatory genes were reduced, and the muscularis externa profile is shaped toward a proinflammatory status. Further, denervation reduced MMs anti-inflammatory genes also in the early phase of POI. Finally, reduced leukocyte infiltration into the muscularis led to a quicker recovery of bowel motility in the late phase of POI.
Keyphrases
- anti inflammatory
- inflammatory response
- rna seq
- oxidative stress
- patients undergoing
- flow cytometry
- single cell
- patient safety
- lipopolysaccharide induced
- type diabetes
- diabetic rats
- high resolution
- high throughput
- lps induced
- mass spectrometry
- cystic fibrosis
- skeletal muscle
- insulin resistance
- atomic force microscopy
- staphylococcus aureus
- high fat diet induced
- heat shock
- single molecule
- heat shock protein