TGF-beta 1 Reduces Neutrophil Adhesion and Prevents Acute Vaso-Occlusive Processes in Sickle Cell Disease Mice

Author(s)

Torres, Lidiane S. ; Chweih, Hanan ; Fabris, Fernanda C. Z. ; Gotardo, Erica M. F. ; Leonardo, Flavia C. ; Olalla Saad, Sara T. ; Costa, Fernando F. ; Conran, Nicola

• Document type: Journal article
• Source: CELLS; v. 11, n. 7, p. 12-pg., 2022-04-01.

Abstract

Sickle cell disease (SCD) patients experience chronic inflammation and recurrent vaso-occlusive episodes during their entire lifetime. Inflammation in SCD occurs with the overexpression of several inflammatory mediators, including transforming growth factor beta-1 (TGF-beta 1), a major immune regulator. In this study, we aimed to investigate the role played by TGF-beta 1 in vascular inflammation and vaso-occlusion in an animal model of SCD. Using intravital microscopy, we found that a daily dose of recombinant TGF-beta 1 administration for three consecutive days significantly reduced TNF alpha-induced leukocyte rolling, adhesion, and extravasation in the microcirculation of SCD mice. In contrast, immunological neutralization of TGF-beta, in the absence of inflammatory stimulus, considerably increased these parameters. Our results indicate, for the first time, that TGF-beta 1 may play a significant ameliorative role in vascular SCD pathophysiology, modulating inflammation and vaso-occlusion. The mechanisms by which TGF-beta 1 exerts its anti-inflammatory effects in SCD, however, remains unclear. Our in vitro adhesion assays with TNF alpha-stimulated human neutrophils suggest that TGF-beta 1 can reduce the adhesive properties of these cells; however, direct effects of TGF-beta 1 on the endothelium cannot be ruled out. Further investigation of the wide range of the complex biology of this cytokine in SCD pathophysiology and its potential therapeutical use is needed. (AU)

• FAPESP's process: 19/18886-1 - Pathophysiological mechanisms and treatment of red blood cell abnormalities
• Grantee: Fernando Ferreira Costa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches
• Grantee: Fernando Ferreira Costa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/14594-0 - TGF-beta action on leukocyte polarization in sickle cell anemia
• Grantee: Lidiane de Souza Torres
• Support Opportunities: Scholarships in Brazil - Post-Doctoral