Abstract
Bacterial and viral infection is a common cause of pneumonia, respiratory failure, and even acute respiratory distress syndrome. Increasing evidence indicates that red blood cells (RBCs) may contribute to immune response and inflammation. However, the precise molecular mechanisms that link RBC and hemolysis to the development and progression of inflammatory pathologies are not entirely understood. In this study, we used bacterial endotoxin, lipopolysaccharide (LPS), to mimic an infectious hemolysis and found that RBCs dynamically regulated cell aggregation between immune cells and human lung microvascular endothelial cells (HLMVEC). When RBCs were treated with LPS, integrin α4β1 was increased and was accompanied by cytokines and chemokines release (TNF-α, IL-1β, IL-6, IL-8, IFN-γ, CXCL12, CCL5, CCL7 and CCL4). Upon α4β1 elevation, RBCs not only facilitated mature monocyte derived dendritic cell (mo-DCs) adhesion but also promoted HLMVEC aggregation. Furthermore, co-culture of the supernatant of LPS pre-treated RBCs with mo-DCs could promote naïve CD4 T cell proliferation. Notably, the filtered culture from LPS-lysed RBCs further promoted mo-DCs migration in a concentration dependent manner. From a therapeutic perspective, cyclic peptide inhibitor of integrin α4β1 combined with methylprednisolone (α4β1/Methrol) remarkably blocked RBCs aggregation to mo-DCs, HLMVEC, or mo-DCs and HLMVEC mixture. Moreover, α4β1/Methrol dramatically reduced mo-DCs migration up-regulated glucocorticoid-induced leucine zipper in mo-DCs, and ultimately reversed immune cell dysfunction induced by hemolysis. Taken together, these results indicate that integrin α4β1 on RBCs could mediate cell-cell interaction for adaptive immunity through influencing cell adhesion, migration, and T cell proliferation.
Highlights
Red blood cells (RBCs) are emerging as important modulators of the innate and adaptive immune response (Anderson et al, 2018)
To investigate the interaction of RBCs and immune cells, we examined the effects of RBCs on immune cells including mo-dendritic cells (DC), human lung microvascular endothelia cell (HLMVEC), and T cells
We found that RBCs in hemolysis increased their adhesive abilities to aggregate with mature monocyte derived dendritic cell (mo-DC), HLMVEC, and T cells
Summary
Red blood cells (RBCs) are emerging as important modulators of the innate and adaptive immune response (Anderson et al, 2018). RBCs are not considered as adhesive cells though they express a large number of adhesion molecules (Pretini et al, 2019). Chaar et al reported that mononuclear cells and RBCs could aggregate together through cell adhesion molecule interaction in SCD (Chaar et al, 2010). Both mature RBCs and reticulocytes were involved in these aggregations through interaction with mononuclear cells, monocytes. Schӓkel and colleagues have shown ex vivo that an excess of RBCs, mimicking the physiological conditions in the blood, could completely prevent the phenotypical maturation of the proinflammatory subset of circulating dendritic cells (DCs) (Schäkel et al, 2006). This response is accentuated with storage duration and partially attenuated with leukoreduction (Chaar et al, 2010)
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.
