Surgically induced leukocytic infiltrates within the rat intestinal muscularis mediate postoperative ileus.
OBJECTIVE
Postoperative ileus is a poorly understood and common problem. We previously demonstrated an association between a suppression in jejunal circular muscle activity and a massive extravasation of leukocytes into the muscularis after surgical manipulation of the small bowel. This study was pursued to establish a direct causal link between these events.


METHODS
Reverse-transcription polymerase chain reaction and immunohistochemistry were used to detect and localize expression of adhesion molecules: P-selectin, intercellular adhesion molecule 1 (ICAM-1), and lymphocyte function-associated antigen 1 (LFA-1). Leukocyte infiltration and in vitro jejunal circular muscle function were quantified in controls and manipulated animals with and without antibody treatment (1A29, WT.1, and WT.3).


RESULTS
Surgical manipulation caused a significant up-regulation within the muscularis of ICAM-1 and P-selectin messenger RNA. ICAM-1 and P-selectin protein expression was increased within the muscularis microvasculature, and ICAM-1 and LFA-1 were expressed on infiltrating cells. Administration of adhesion molecule antibodies prevented the recruitment of monocytes and neutrophils into the muscularis and also averted jejunal circular muscle dysfunction.


CONCLUSIONS
The data demonstrate that adhesion molecule antibodies prevent surgically induced suppression of intestinal muscle contractions and therefore suggests that late postoperative ileus is mediated through a leukocytic inflammatory response within the intestinal muscularis externa.
Departments of Surgery and Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
J C
JC
Kalff
T M
TM
Carlos
W H
WH
Schraut
T R
TR
Billiar
R L
RL
Simmons
A J
AJ
Bauer
D000818:Animals; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology; D007415:Intestinal Obstruction / Q000209:etiology*; D007422:Intestines / Q000473:pathology*; D007962:Leukocytes / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008297:Male; D009130:Muscle, Smooth / Q000473:pathology*; D019007:P-Selectin / Q000235:genetics / Q000502:physiology; D011183:Postoperative Complications / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011912:Rats, Inbred ACI
D016169:Lymphocyte Function-Associated Antigen-1; D019007:P-Selectin; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1