DOI: 10.1101/508366Jan 2, 2019Paper

Effect of Adhesion and Substrate Elasticity on Neutrophil Extracellular Trap Formation

BioRxiv : the Preprint Server for Biology
Luise ErpenbeckSebastian Kruss

Abstract

Neutrophils are the most abundant type of white blood cells. As part of their immune defense mechanisms they are able to decondense and release their chromatin as neutrophil extracellular traps (NETs). This process (NETosis) also plays an important role in many chronic and inflammatory diseases such as atherosclerosis, rheumatoid arthritis, diabetes and cancer. For this reason, much effort has been invested into understanding biochemical signaling pathways in NETosis. However, the impact of the mechanical micro-environment and adhesion on NETosis is not well understood. Here, we study how adhesion and especially substrate elasticity affect NETosis. We employed polyacrylamide gels with varied elasticity (Young's modulus E) within the physiologically relevant range from 1 kPa to 128 kPa and coated the gels with integrin ligands (collagen I, fibrinogen). Neutrophils were cultured on these substrates and stimulated with chemical inducers of NETosis: phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS). Interestingly, PMA-induced NETosis was neither affected by substrate elasticity nor by different integrin ligands. In contrast, for LPS stimulation, NETosis rates increased with increasing substrate elasticity (E > 20 k...Continue Reading

Related Concepts

Tissue Adhesions
Affect (Mental Function)
Rheumatoid Arthritis
Atherosclerosis
Malignant Neoplasms
Chromatin
Chronic Disease
Collagen
Diabetes
Environment

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