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Updated: Jul 31, 2026

Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Lipopolysaccharide activates the muscularis macrophage network and suppresses circular smooth muscle activity
M K Eskandari1, J C Kalff, T R Billiar
1Department of Surgery, University of Pittsburgh Medical School, Pennsylvania 15261, USA.
Abstract:
Bacterial lipopolysaccharide (LPS) is a causative agent of sepsis-induced ileus. Although it is known that LPS activates macrophages and initiates inflammation, the consequences of LPS on the macrophage network and a potential inflammatory response within the intestinal muscularis have not been investigated. This study was designed to identify cellular and functional changes in rat intestinal muscularis after intraperitoneal LPS. Histo- and immunohistochemistry were used to phenotype leukocytes. Functional alterations were determined using an organ bath. Compared with controls, LPS caused a 21-fold increase in staining for the lymphocyte activation marker-1 (LFA-1) localized to the ED2+ macrophage network 1 h after injection. This was followed by a significant infiltration of neutrophils, mast cells, and monocytes into the muscularis. LPS also caused a 62% reduction in spontaneous circular muscle activity and a 91% suppression of bethanechol-stimulated contractions 12 h after injection. These results demonstrate that endotoxemia 1) acutely activates the muscularis macrophage network, 2) causes the extravasation of leukocytes, and 3) results in circular muscle impairment.
Insights
Bacterial lipopolysaccharide (LPS) causes sepsis-induced ileus by activating macrophages and leading to inflammation. This study reveals LPS impairs intestinal muscle function and increases leukocyte infiltration in rats.
Area of Science:
- Gastroenterology
- Immunology
- Cellular Biology
Background:
- Bacterial lipopolysaccharide (LPS) triggers inflammation and is linked to sepsis-induced ileus.
- The impact of LPS on intestinal muscularis macrophages and inflammation remains under-investigated.
Purpose of the Study:
- To investigate cellular and functional changes in rat intestinal muscularis following LPS administration.
- To understand the role of the macrophage network in LPS-induced intestinal dysfunction.
Main Methods:
- Histology and immunohistochemistry to identify leukocyte populations.
- Organ bath studies to assess intestinal muscle contractility.
- Intraperitoneal LPS injection in a rat model.
Main Results:
- LPS significantly increased lymphocyte activation marker-1 (LFA-1) on macrophages within 1 hour.
- Neutrophil, mast cell, and monocyte infiltration into the muscularis was observed.
- A 62% reduction in spontaneous and 91% suppression of stimulated circular muscle activity occurred 12 hours post-LPS.
Conclusions:
- Endotoxemia acutely activates the intestinal muscularis macrophage network.
- LPS induces leukocyte extravasation into the muscularis.
- LPS exposure leads to significant impairment of intestinal circular muscle function.
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