Age Increases Monocyte Adhesion on Collagen

Samira Khalaji,Kay-E Gottschalk,Medhanie A Mulaw,Fenneke Kleinjan,Jochen H Weishaupt,Karin M Danzer,Lisa Zondler,Ulla Nolte

doi:10.1038/srep46532

Abstract

Adhesion of monocytes to micro-injuries on arterial walls is an important early step in the occurrence and development of degenerative atherosclerotic lesions. At these injuries, collagen is exposed to the blood stream. We are interested whether age influences monocyte adhesion to collagen under flow, and hence influences the susceptibility to arteriosclerotic lesions. Therefore, we studied adhesion and rolling of human peripheral blood monocytes from old and young individuals on collagen type I coated surface under shear flow. We find that firm adhesion of monocytes to collagen type I is elevated in old individuals. Pre-stimulation by lipopolysaccharide increases the firm adhesion of monocytes homogeneously in older individuals, but heterogeneously in young individuals. Blocking integrin αx showed that adhesion of monocytes to collagen type I is specific to the main collagen binding integrin αxβ2. Surprisingly, we find no significant age-dependent difference in gene expression of integrin αx or integrin β2. However, if all integrins are activated from the outside, no differences exist between the age groups. Altered integrin activation therefore causes the increased adhesion. Our results show that the basal increase in integrin activation in monocytes from old individuals increases monocyte adhesion to collagen and therefore the risk for arteriosclerotic plaques.

Highlights

To assess the rolling behaviour of monocytes in different individuals based on age, we counted the number of monocytes which rolled on the collagen type I substrate of micro-fluidic chamber
Our result show that the number of rolling monocyte is unaffected by age in different individuals (Fig. 1A)
Monocytes contribute to immune surveillance and the inflammatory responses in inflammatory diseases such as atherosclerosis

Summary

Introduction

Monocytes from older individuals respond to LPS homogenously in contrast to monocytes from young individuals, where strong individual-to-individual differences are observed. Rolling of monocytes seems to be unaffected by age and LPS stimulation. Since monocyte adhesion is strongly mediated by integrins, we went on to test integrin expression. Neither we nor others[10] found an increase in the expression of integrins specific for collagen type I. The observed increase in adhesion of monocytes from older individuals is either integrin-independent or caused by altered signalling pathways leading to an increase in integrin activation

Methods

Results

Conclusion