Original Article
Copyright ©2010 Baishideng. All rights reserved
World J Gastroenterol. Jun 7, 2010; 16(21): 2648-2656
Published online Jun 7, 2010. doi: 10.3748/wjg.v16.i21.2648
Prophylactic uses of integrin CD18-βA peptide in a murine polymicrobial peritonitis model
Kwong-Fai Wong, Jana Wo, David Ho, Ronnie T Poon, José M Casasnovas, John M Luk
Kwong-Fai Wong, John M Luk, Department of Pharmacology and Surgery, National University Hospital System, National University of Singapore, Singapore 117597, Singapore
Kwong-Fai Wong, Jana Wo, David Ho, Ronnie T Poon, John M Luk, Department of Surgery, Queen Mary Hospital, Pokfulam, HKSAR, Hong Kong, China
José M Casasnovas, Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma, 28049 Madrid, Spain
Author contributions: Wong KF performed the experiments, analyzed the data and wrote the paper; Wo J and Ho D performed the experiments; Poon RT and Casasnovas JM designed the study; Luk JM initiated and designed the study, analyzed the data and wrote the paper.
Supported by Research Grants Council of Hong Kong, National University of Singapore and NMRC
Correspondence to: Dr. Kwong-Fai Wong, Department of Pharmacology and Surgery, National University Hospital System, National University of Singapore, Singapore 117597, Singapore. tonywkf@hku.hk
Telephone: +65-65164516 Fax: +65-68737690
Received: February 5, 2010
Revised: March 2, 2010
Accepted: March 9, 2010
Published online: June 7, 2010
Abstract

AIM: To evaluate the prophylactic properties of integrin CD18-βA peptide in a murine model of abdominal polymicrobial peritonitis and sepsis.

METHODS: Bacterial sepsis was induced in Institute of Cancer Research (ICR) mice by cecal ligation and puncture (CLP) surgery. Inflicted mice were then injected with either sterile saline or CD18-βA peptide intraperitoneally at 2 h after surgery, and were sacrificed at 12 and 24 h after surgery. Blood samples were immediately collected, and analyzed for endotoxin activity and tumor necrosis factor (TNF)-α and interleukin (IL)-6. Lungs and liver were studied for CD45+ leukocyte and CD3 mRNA content. Pulmonary expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM) and E-selectin was also determined.

RESULTS: Intraperitoneal injection of CD18-βA peptide significantly suppressed circulating endotoxin activity (P < 0.01) at 24 h, as well as serum levels of TNF-α (P < 0.05 at 12 and 24 h) and IL-6 (P < 0.01 at 12 h, P < 0.05 at 24 h) in CLP-inflicted mice. CD18-βA peptide also abrogated leukocyte infiltration into liver and lungs as unveiled by reduced CD45+ leukocyte and CD3 mRNA contents. Furthermore, the peptide significantly reduced pulmonary expression of VCAM (P < 0.01 at 12 h, P < 0.001 at 24 h), E-selectin (P < 0.01 at 12 and 24 h), and ICAM-1 (P < 0.01 at 12 h, P < 0.001 at 24 h). These actions of CD18-βA peptide collectively protected septic mice against lethality (P < 0.01).

CONCLUSION: CD18-βA peptide is a potent endotoxin antagonist that can protect surgical patients against sepsis-associated lethality.

Keywords: Bacterial endotoxin; Integrin CD18; Inflammation; Biotherapeutic peptide