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

Hum Immunol. 2009 Apr;70(4):211-7. doi: 10.1016/j.humimm.2009.01.026. Epub 2009 Feb 7.


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)-gamma and lipopolysaccharide, which promote classical M1 macrophage activation affected expression of NRP-1, NRP-2 and plexin A1. IFN-gamma 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Line
  • Flow Cytometry
  • Gene Expression Profiling*
  • Humans
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / physiology
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology
  • Neuropilin-1 / genetics*
  • Neuropilin-1 / metabolism
  • Neuropilin-1 / physiology
  • Neuropilin-2 / genetics
  • Neuropilin-2 / metabolism
  • Neuropilin-2 / physiology
  • Phagocytosis
  • Protein Binding
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Cell Surface / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Semaphorin-3A / genetics*
  • Semaphorin-3A / metabolism
  • Semaphorin-3A / physiology


  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Neuropilin-2
  • PLXNA1 protein, human
  • PLXNA2 protein, human
  • PLXNA3 protein, human
  • Receptors, Cell Surface
  • Semaphorin-3A
  • Neuropilin-1
  • Macrophage Colony-Stimulating Factor
  • Interferon-gamma