Role of Substance P-Dependent Chemotactic Signaling in Postoperative Adhesion Formation.

Autor: Kosaka H; Department of Surgery, Kansai Medical University, Hirakata, Osaka, JAPAN. Electronic address: kosakahi@hirakata.kmu.ac.jp., Kaibori M; Department of Surgery, Kansai Medical University, Hirakata, Osaka, JAPAN., Chu DI; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL., Stucchi AF; Department of Surgery, Boston University School of Medicine, Boston, MA., Sekimoto M; Department of Surgery, Kansai Medical University, Hirakata, Osaka, JAPAN.
Jazyk: angličtina
Zdroj: The Journal of surgical research [J Surg Res] 2022 Feb; Vol. 270, pp. 49-57. Date of Electronic Publication: 2021 Oct 09.
DOI: 10.1016/j.jss.2021.08.038
Abstrakt: Background: Postoperative adhesions are a potentially life-threatening complication of abdominal surgery. We previously showed that substance P (SP), acting through the neurokinin-1 receptor (NK-1R), is an important early mediator of adhesiogenesis through its regulation of the tissue plasminogen activator/plasminogen activator inhibitor-1 (PAI-1) fibrinolytic system. SP also mediates neurogenic inflammation by recruiting inflammatory leukocytes, such as neutrophils and macrophages. Our objective was to determine the role of SP-dependent chemotactic recruitment of these inflammatory cells through the CXCR2 in postsurgical adhesion formation.
Materials and Methods: A mouse cecal cauterization model was used to generate intra-abdominal adhesions. Protein and mRNA levels of the chemokines CXCL1 and CXCL2 and their receptor CXCR2 were measured at 3 h and 6 h after surgery in peritoneal tissue and in peritoneal lavages in response to antagonists for the SP receptor and CXCR2, and in IFN-γ knockout mice.
Results: Postsurgical adhesion formation was inhibited by both an antagonist to NK-1R and an antagonist to CXCR2. Expression levels of neutrophil chemokines and CXCR2 in peritoneal tissue peaked 3-6 h after surgery and partially depended on SP and IFN-γ, one of its downstream mediators. An NK-1R antagonist inhibited SP-mediated increases in the expression of the PAI-1 inhibitory component of the fibrinolytic system, but the CXCR2 antagonist had no effect.
Conclusions: Postsurgical adhesiogenesis involves upregulation of chemokine signaling that is partially SP- and IFN-γ-dependent. However, the adhesiogenic properties of chemokine signaling are not mediated through the inhibition of fibrinolysis with PAI-1, as was previously shown for SP.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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