Abstract
BackgroundPentraxins 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.ResultsWe 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.ConclusionThese data reveal differential signaling by pentraxins on immune cells, and suggest that CRP can regulate the proliferation of some myeloid leukemia cells.
Highlights
Pentraxins are a family of highly conserved secreted proteins that regulate the innate immune system, including monocytes and macrophages
The effect of C-reactive protein (CRP) on Mono Mac 6 cells appears to be dependent on CD64 (FcγRI) and the IgA receptor (FcαR; CD89), and is negatively regulated by a phosphatidylinositol-3-kinase (PI3K) dependent pathway. These data reveal differential signaling by pentraxins on immune cells, and suggest that CRP may be a novel regulator of some subtypes of leukemia
CRP inhibits the proliferation of mono Mac 6 cells Since pentraxin receptors are expressed on monocytes, an intriguing possibility is that pentraxins might affect the proliferation or viability of some monocyte-derived leukemia cell lines
Summary
Pentraxins are a family of highly conserved secreted proteins that regulate the innate immune system, including monocytes and macrophages. Pentraxins are a family of highly conserved secreted proteins that regulate the innate immune system, including cells of myeloid lineage such as neutrophils, monocytes, and macrophages [1,2,3]. SAP and PTX3 can affect tumors, either by regulating cancer-related inflammation, angiogenesis, or directly inhibiting cancer cell growth and differentiation [9, 23,24,25,26]. Elevated serum CRP levels are associated with poor prognosis in solid tumors, probably as an indicator of chronic inflammation associated with tumor progression, but the role of CRP in leukemia is unclear [27, 28]
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