Expression and function of semaphorin 3A and its receptors in human monocyte-derived macrophages

Jong Dae Ji, Kyung Hyun Park-Min, Lionel B. Ivashkiv

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Semaphorins are a large family of secreted and membrane-bound proteins. Recently, several roles of semaphorins in the immune system have emerged. Several semaphorins and their receptors are expressed in a variety of lymphoid and myeloid cells and affect immune cell functions, including cell proliferation, differentiation, chemotaxis, and cytokine production. However, the roles of class 3 semaphorins in human myeloid cells are not well known. Here we examined the regulation of expression of class 3 semaphorins and their receptors by inflammatory stimuli and their function in human macrophages. We show that the expression of Sema3A receptors (neuropilin-1 (NRP-1), NRP-2, plexin A1, plexin A2, and plexin A3) significantly increased during M-CSF-mediated differentiation of monocytes into macrophages under conditions that promote an M2 alternatively activated macrophage phenotype. Consistent with increased NRP-1 expression, cell surface binding of Sema3A increased during M2 differentiation. Interferon (IFN)-γ and lipopolysaccharide, which promote classical M1 macrophage activation affected expression of NRP-1, NRP-2 and plexin A1. IFN-γ decreased NRP-1 expression and LPS suppressed NRP-2 and plexin A1 expression. Furthermore we show that Sema3A induced apoptosis in monocyte-derived macrophages and cooperated with anti-Fas CH11 antibody to augment apoptosis. Our results suggest that Sema3A plays a role in induction of apoptosis in monocyte-derived macrophages that are resistant to Fas-induced apoptosis, and that its function can be modulated in inflammatory conditions.

Original languageEnglish
Pages (from-to)211-217
Number of pages7
JournalHuman Immunology
Volume70
Issue number4
DOIs
Publication statusPublished - 2009 Apr 1

Fingerprint

Semaphorin-3A
Semaphorins
Neuropilin-1
Macrophages
Apoptosis
Myeloid Cells
Interferons
Macrophage Colony-Stimulating Factor
Macrophage Activation
Chemotaxis
varespladib methyl
Lipopolysaccharides
Monocytes
Cell Differentiation
Immune System
Membrane Proteins
Cell Proliferation
plexin
Lymphocytes
Cytokines

Keywords

  • Macrophages
  • Neuropilin
  • Plexin
  • Semaphorin

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Expression and function of semaphorin 3A and its receptors in human monocyte-derived macrophages. / Ji, Jong Dae; Park-Min, Kyung Hyun; Ivashkiv, Lionel B.

In: Human Immunology, Vol. 70, No. 4, 01.04.2009, p. 211-217.

Research output: Contribution to journalArticle

Ji, Jong Dae ; Park-Min, Kyung Hyun ; Ivashkiv, Lionel B. / Expression and function of semaphorin 3A and its receptors in human monocyte-derived macrophages. In: Human Immunology. 2009 ; Vol. 70, No. 4. pp. 211-217.
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