Abstract
Leukocyte recruitment is one of the most important cellular responses to tissue damage. Leukocyte extravasation is exquisitely regulated by mechanisms of selective leukocyte-endothelium recognition through adhesion proteins in the endothelial cell surface that recognize specific integrins in the activated leukocytes. A similar mechanism is used by tumor cells during metastasis to extravasate and form a secondary tumor. Nitric oxide (NO) has been classically described as an anti-inflammatory molecule that inhibits leukocyte adhesion. However, the evidence available shows also a positive role of NO in leukocyte adhesion. These apparent discrepancies might be explained by the different NO concentrations reached during the inflammatory response, which are highly modulated by the expression of different nitric oxide synthases, along the inflammatory response and by changes in their subcellular locations.
Highlights
Reviewed by: Nicola Conran, Campinas State University, Brazil Carlos Cabañas, Consejo Superior de Investigaciones Científicas (CSIC), Spain
Initial contact and rolling steps are initiated by endothelial cell leukocyte adhesion molecule-1 (ELAM-1, E-selectin) and P-selectin, which are expressed in the endothelium and bind to L-selectin, PSGL-1, CD44, CD43, and ESL-1 in the leukocyte
It is reasonable to state that, in non-stimulated cells, Nitric oxide (NO) concentration maintains an anti-adhesive phenotype at the endothelial cell membrane – inasmuch as inhibition of NOS causes increased leukocyte adhesion
Summary
The effects of NO on leukocyte adhesion are related to transcriptional regulation of adhesion proteins expression on the endothelium (De Caterina et al, 1995; Khan et al, 1996; Liu et al, 1998; Lefer et al, 1999; Waldow et al, 2006; Buckanovich et al, 2008; Carreau et al, 2011; Stojak et al, 2018). In non-stimulated cells, basal NO production generated by eNOS located to the Golgi and caveolae (Feron and Balligand, 2006; Zhang et al, 2006) will maintain an anti-adhesive phenotype in part by basal S-nitrosylation of NSF and by inhibiting ICAM-1 clustering (Feron and Balligand, 2006; Zhang et al, 2006; Lowenstein, 2007; Mukhopadhyay et al, 2008; Gao et al, 2018; Figure 4A). The combined effects of releasing the inhibition induced by basal NO on vesicular transport and clustering, plus the active stimulation by NO of pathways that increase vesicular transport and clustering, will induce leukocyte adhesion at short times of simulation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
