Expression and regulation of murine macrophage angiopoietin-2

Neil Hubbard, Debora Lim, Mithia Mukutmoni, Ann Cai, Kent L Erickson

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Our understanding of angiogenesis has increased significantly in the past few years with the discovery of angiopoietins (Ang). Specifically, Ang2 has been associated with pathologic as well as normal vascularization. While previous studies have shown that a major source of Ang2 has been endothelial cells and tumor cells, we reasoned that macrophages would also have the ability to express angiopoietins, specifically Ang2, due to that cell's role in wound healing, tumor angiogenesis, and a number of non-oncological diseases, such as rheumatoid arthritis and psoriasis. In this study, murine macrophages constitutively expressed both transcripts and protein for Ang2 but not Ang1 or Ang3. The secretion of Ang2 was enhanced by treatment with lipopolysaccharide, interferon-γ, prostaglandin E2 and other cyclic AMP-elevating agents, as well as vascular endothelial growth factor (VEGF). Cyclic AMP-dependent protein kinase (PKA) played a major role in this enhancement since the PKA inhibitor, H89, blocked secretion of Ang2. Since stimulation of the PKA pathway can lead to macrophage production of VEGF, it is possible that enhancement of Ang2 production by macrophages may be due to autocrine responsiveness to VEGF. Adding anti-VEGF antibodies to the supernatants of stimulated macrophages blocked secretion of Ang2. This study is the first to show murine macrophage production of Ang2 and to provide evidence that it can be regulated. Understanding the regulation of macrophage Ang2 production is especially important in an effort to target the pathologic role of macrophages while preserving their role in immunity and homeostasis.

Original languageEnglish (US)
Pages (from-to)102-109
Number of pages8
JournalCellular Immunology
Volume234
Issue number2
DOIs
StatePublished - Apr 2005

Fingerprint

Angiopoietin-2
Macrophages
Vascular Endothelial Growth Factor A
Angiopoietins
Protein Kinase Inhibitors
Cyclic AMP-Dependent Protein Kinases
Psoriasis
Dinoprostone
Cyclic AMP
Wound Healing
Protein Kinases
Interferons
Lipopolysaccharides
Immunity
Rheumatoid Arthritis
Neoplasms
Homeostasis
Endothelial Cells
Antibodies

Keywords

  • Angiopoietin-2
  • Macrophages
  • PKA pathway
  • Prostaglandin
  • VEGF

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Expression and regulation of murine macrophage angiopoietin-2. / Hubbard, Neil; Lim, Debora; Mukutmoni, Mithia; Cai, Ann; Erickson, Kent L.

In: Cellular Immunology, Vol. 234, No. 2, 04.2005, p. 102-109.

Research output: Contribution to journalArticle

Hubbard, Neil ; Lim, Debora ; Mukutmoni, Mithia ; Cai, Ann ; Erickson, Kent L. / Expression and regulation of murine macrophage angiopoietin-2. In: Cellular Immunology. 2005 ; Vol. 234, No. 2. pp. 102-109.
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