Negative regulation of monocyte adhesion to arterial elastic laminae by signal regulatory protein α and Src homology 2 domain-containing protein-tyrosine phosphatase-1

Shu Q. Liu*, Paul K. Alkema, Christopher Tieché, Brandon J. Tefft, Diana Z. Liu, Yan Chun Li, Bauer E. Sumpio, Joseph A. Caprini, Mary Paniagua

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Elastic laminae are extracellular matrix constituents that not only contribute to the stability and elasticity of arteries but also play a role in regulating arterial morphogenesis and pathogenesis. We demonstrate here that an important function of arterial elastic laminae is to prevent monocyte adhesion, which is mediated by the inhibitory receptor signal regulatory protein (SIRP) α and Src homology 2 domain-containing protein-tyrosine phosphatase (SHP)-1. In a matrix-based arterial reconstruction model in vivo, elastic laminae were resistant to leukocyte adhesion and transmigration compared with the collagen-dominant arterial adventitia. The density of leukocytes within the elastic lamina-dominant media was about 58 -70-fold lower than that within the adventitia from 1 to 30 days. An in vitro assay confirmed the inhibitory effect of elastic laminae on monocyte adhesion. The exposure of monocytes to elastic laminae induced activation of SIRP α, which in turn activated SHP-1. Elastic lamina degradation peptides extracted from arterial specimens could also activate SIRP α and SHP-1. The knockdown of SIRP α and SHP-1 by specific small interfering RNA diminished the inhibitory effect of elastic laminae, resulting in a significant increase in monocyte adhesion. These observations suggest that SIRP α and SHP-1 potentially mediate the inhibitory effect of elastic laminae on monocyte adhesion.

Original languageEnglish (US)
Pages (from-to)39294-39301
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number47
DOIs
StatePublished - Nov 25 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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