Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0908536 on April 28, 2009

Published online before print April 28, 2009
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(Journal of Leukocyte Biology. 2009;86:381-388.)
© 2009 Society for Leukocyte Biology

Hypoxia increases macrophage motility, possibly by decreasing the heparan sulfate proteoglycan biosynthesis

Annika Asplund*, Gunnel Östergren-Lundén*, Germán Camejo*,{dagger}, Pia Stillemark-Billton* and Göran Bondjers*,{ddagger},1

* Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden;
{ddagger} Nordic School of Public Health, Göteborg, Sweden; and
{dagger} AstraZeneca R & D, Mölndal, Sweden

1. Correspondence: Nordic School of Public Health, Box 12133, 402 42 Göteborg, Sweden. E-mail: bondjers{at}nhv.se

ABSTRACT

Macrophages are recruited and retained in hypoxic sites in atherosclerotic lesions and tumors. Furthermore, macrophages are suggested to be a major source of HSPG synthesis in atherosclerotic lesions. HSPG are, among other things, known to regulate cell motility, cell adhesion, and receptor interaction. The aim of this study was to investigate the effect of hypoxia on HSPG expression and macrophage motility. We also explored the potential regulation of HSPG by the transcription factor HIF-1{alpha}. The nondirected cell motility was increased in HMDM after 24 h exposure to hypoxia (0.5% O2) compared with normal cell culture condition (21% O2). Enzymatic degradation of HS GAG further increased the motility of the HMDM in hypoxia, indicating a role of reduced cell-associated HSPG in the increased HMDM motility. HMDM exposed to 24 h of hypoxia had lower mRNA expressions of syndecan-1 and –4 compared with cells exposed to normal cell culture conditions. Protein levels of syndecan-1 were also decreased significantly in response to hypoxia, and cells subjected to hypoxia had lower mRNA expression for key enzymes involved in HS biosynthesis. In addition, hypoxia was found to reduce the relative content of HS GAG. Transfecting THP-1 cells with siHIF-1{alpha} indicated that this transcription factor was not involved in the hypoxia-induced modifications of HSPG expression. Given the documented multiple functions of HSPG in macrophage behavior, the hypoxia-induced modifications of HSPG may be of relevance for the development of atherosclerotic lesions and tumor progression.

Key Words: leukocytes • oxygen deprivation • membrane-sulfated polysaccharides




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A. Asplund, P. Stillemark-Billton, E. Larsson, E. K. Rydberg, J. Moses, L. M. Hulten, B. Fagerberg, G. Camejo, and G. Bondjers
Hypoxic regulation of secreted proteoglycans in macrophages
Glycobiology, January 1, 2010; 20(1): 33 - 40.
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