Lipopolysaccharide activates the muscularis macrophage network and suppresses circular smooth muscle activity.
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.
Eskandari
M K
MK
Department of Surgery, University of Pittsburgh Medical School, Pennsylvania 15261, USA.
Kalff
J C
JC
Billiar
T R
TR
Lee
K K
KK
Bauer
A J
AJ
D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D017931:DNA Primers; D004553:Electric Conductivity; D019446:Endotoxemia / Q000503:physiopathology*; D007583:Jejunum / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000032:analysis / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009000:Monocytes / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology; D016133:Polymerase Chain Reaction; D051381:Rats; D011912:Rats, Inbred ACI; D013997:Time Factors
D017931:DNA Primers; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D018723:Bethanechol