C-reactive protein (CRP) but not the related pentraxins serum amyloid P and PTX3 inhibits the proliferation and induces apoptosis of the leukemia cell line Mono Mac 6

BMC Immunol. 2017 Dec 4;18(1):47. doi: 10.1186/s12865-017-0230-z.

Abstract

Background: Pentraxins are a family of highly conserved secreted proteins that regulate the innate immune system, including monocytes and macrophages. C-reactive protein (CRP) is a plasma protein whose levels can rise to 1000 μg/ml from the normal <3 μg/ ml during inflammation.

Results: We find that CRP inhibits proliferation of the human myeloid leukemia cell line Mono Mac 6 with an IC50 of 75 μg/ ml by inducing apoptosis of these cells. The related proteins serum amyloid P (SAP) and pentraxin 3 (PTX3) do not inhibit Mono Mac 6 proliferation. CRP has no significant effect on the proliferation of other leukemia cell lines such as HL-60, Mono Mac 1, K562, U937, or THP-1, or the survival of normal peripheral blood cells. The effect of CRP appears to be dependent on the CRP receptor FcγRI, and is negatively regulated by a phosphatidylinositol -3-kinase pathway.

Conclusion: These data reveal differential signaling by pentraxins on immune cells, and suggest that CRP can regulate the proliferation of some myeloid leukemia cells.

Keywords: Apoptosis; C reactive protein; Leukemia; Pentraxin.

MeSH terms

  • Antigens, CD / metabolism
  • Apoptosis / drug effects*
  • C-Reactive Protein / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Leukemia, Myeloid, Acute / physiopathology*
  • Leukocytes, Mononuclear / drug effects
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, Fc / genetics
  • Receptors, Fc / metabolism
  • Receptors, IgG / metabolism
  • Receptors, Immunologic / genetics
  • Serum Amyloid P-Component / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Antigens, CD
  • CRP protein, human
  • Fc(alpha) receptor
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, Fc
  • Receptors, IgG
  • Receptors, Immunologic
  • Serum Amyloid P-Component
  • PTX3 protein
  • C-Reactive Protein
  • Phosphatidylinositol 3-Kinase