Surgically induced leukocytic infiltrates within the rat intestinal muscularis mediate postoperative ileus

doi:10.1053/gast.1999.0029900378

Gastroenterology

Volume 117, Issue 2, August 1999, Pages 378-387

https://doi.org/10.1053/gast.1999.0029900378 Get rights and content

Abstract

Background & Aims: 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.

Section snippets

Animals

A×C 9935 Irish, inbred strain male rats (ACI) (200-250 g) were obtained from Harlan–Sprague–Dawley (Indianapolis, IN). The protocol was approved by the University of Pittsburgh Institutional Animal Care and Use Committee. Rats were housed in a pathogen-free facility that is accredited by the American Association for Accreditation of Laboratory Animal Care and complies with the requirements of humane animal care as stipulated by the U.S. Department of Agriculture and the Department of Health and

ICAM-1 and P-selectin messenger RNA levels

Surgical manipulation of the small intestine results in a massive recruitment of inflammatory cells into the intestinal muscularis; a major population of the recruited leukocytes consisted of PMNs.¹⁰ An adhesion molecule that plays a central role in the recruitment of numerous leukocyte populations during inflammation is ICAM-1. P-selectin is also known to participate in the early recruitment of PMNs.²⁴ Expression of the adhesion molecules ICAM-1 and P-selectin within the isolated intestinal

Discussion

This study shows that gentle surgical manipulation of the rat small intestine results in a significant up-regulation of adhesion molecules within the vasculature of the rat intestinal muscularis and that this precedes a massive extravasation of leukocytes into the intestinal muscularis. Furthermore, and most importantly, these data show for the first time that the surgically induced cellular inflammatory response (i.e., the extravasation of leukocytes and their secretory products) directly

Acknowledgements

The authors thank Dr. Donald C. Anderson from Pharmacia and Upjohn Inc., Kalamazoo, Michigan, for the generous gift of the adhesion molecule antibodies 1A29, WT.1, and WT.3.

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Surgically induced leukocytic infiltrates within the rat intestinal muscularis mediate postoperative ileus

Abstract

Section snippets

Animals

ICAM-1 and P-selectin messenger RNA levels

Discussion

Acknowledgements

Blood

Gastroenterology

Blood

Immunobiology

Immunol Today

Peptides

J Biol Chem

Gastroenterology

Blood

Postoperative ileus

Dig Dis Sci

Effect of adrenergic and nitrergic blockade on experimental ileus in rats

Br J Pharmacol

Role of CRF in stress-related alterations of gastric and colonic motor function

Ann NY Acad Sci

Early oral feeding after elective colorectal surgery: is it safe?

Trop Gastroenterol

Outcome of laparoscopic colorectal surgery in older patients

Am Surg

Neuropeptides, inflammation, and motility

Dig Dis Sci

Lipopolysac-charide activates the muscularis macrophage network and sup-presses circular smooth muscle activity

Am J Physiol

Phagocyte activation and infiltration of the intestinal muscularis with impairment of small bowel motility after surgical manipulation

Langenbeck Arch Chir

Alterations of intestinal transit time following ischemia-reperfusion injury in the rat

Dig Surg

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Ann Surg