AJP - Gastrointestinal and Liver Physiology, Vol 273, Issue 3 727-G734, Copyright © 1997 by American Physiological Society

ARTICLES

Lipopolysaccharide activates the muscularis macrophage network and suppresses circular smooth muscle activity

M. K. Eskandari, J. C. Kalff, T. R. Billiar, K. K. Lee and A. J. Bauer
Department of Surgery, University of Pittsburgh Medical School, Pennsylvania 15261, USA.

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.

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