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The role of neutrophils in peritoneal adhesion formation
A Ar'Rajab1, W Mileski, J T Sentementes
1Department of Surgery, University of Texas Southwestern Medical Center Dallas 75235-9031, USA.
Abstract:
The most common cause of intraperitoneal adhesions is previous abdominal surgery. Postoperative adhesion formation results from a fibroproliferative inflammatory reaction that begins with an influx of polymorphonuclear leukocytes (PMNs) into the peritoneal cavity. Adherence of the PMNs to the endothelial cells (EC) is necessary for PMN migration into the tissue in response to a stimulus. Several receptor-counterreceptor pairs of ligands such as CD11/CD18 on the PMN and ICAM-1 (CD54) on EC have been identified. Monoclonal antibody against CD11/CD18 (R15.7) inhibits PMN adherence and migration and consequently protects against PMN-induced tissue injuries. We therefore studied the effect of preventing PMN-EC adherence, using anti-CD18 monoclonal antibody, on postoperative adhesion formation in rabbits. Group 1 was a control receiving physiologic saline, and group 2 received anti-CD18 antibody (R15.7, 2 mg/kg). The treatment was administered iv at the end of surgery and repeated on the first and second postoperative days. Peritoneal adhesions were induced at laparotomy by repairing two peritoneal defects, by oversewing the defect (model 1), and by resuturing the removed parietal peritoneum in its place as an ischemic graft (model 2). Adhesions were evaluated blindly at 10 days after operation by measuring the percentage of the suture line covered with adhesions (model 1) or by a scoring system (model 2). All control animals developed intraperitoneal adhesions and the percentage of the suture line covered with adhesions was 25 +/- 5.9% (mean +/- SEM) and the mean score in model 2 was 0.9 +/- 0.2. Anti-CD18 antibody, R15.7, increased the degree of postoperative adhesion formation in both models, but the results were significant only in model 2. Also, anti-CD18 antibody significantly decreased peritoneal neutrophils from 11.1 x 10(7) +/- 1.8 x 10(7) to 2.2 x 10(7) +/- 0.4 x 10(7) (P < 0.001) on the first postoperative day. It is concluded that inhibition of PMN-EC adherence does influence the postoperative adhesion formation. These results might suggest that PMNs have a role in modulating postoperative adhesion formation.
Insights
This study investigated how blocking polymorphonuclear leukocyte (PMN) adherence impacts postoperative adhesion formation. Unexpectedly, inhibiting PMN-endothelial cell adherence with anti-CD18 antibody increased adhesion severity in rabbits, suggesting PMNs modulate adhesion development.
Area of Science:
- Surgical pathology
- Immunology
- Wound healing
Background:
- Intraperitoneal adhesions commonly follow abdominal surgery.
- Adhesion formation involves an inflammatory response with polymorphonuclear leukocytes (PMNs).
- PMN adherence to endothelial cells (ECs) is crucial for migration and tissue injury.
Purpose of the Study:
- To investigate the effect of inhibiting PMN-EC adherence on postoperative adhesion formation.
- To determine if blocking CD11/CD18 interaction influences adhesion development.
Main Methods:
- Rabbits received either saline (control) or anti-CD18 antibody (R15.7).
- Peritoneal adhesions were induced using two surgical models (defect repair and ischemic graft).
- Adhesion formation was evaluated blindly at 10 days post-surgery.
Main Results:
- Anti-CD18 antibody treatment increased postoperative adhesion formation in both models, significantly in the ischemic graft model.
- The antibody significantly reduced peritoneal neutrophils on postoperative day 1.
- Control animals showed significant adhesion formation in both models.
Conclusions:
- Inhibition of PMN-EC adherence influences postoperative adhesion formation.
- These findings suggest a modulatory role for PMNs in the development of postoperative adhesions.
- Targeting PMN-EC interactions may have complex effects on adhesion pathogenesis.