Increased ceruloplasmin expression caused by infiltrated leukocytes, activated microglia, and astrocytes in injured female rat spinal cords

J Neurosci Res. 2018 Jul;96(7):1265-1276. doi: 10.1002/jnr.24221. Epub 2018 Jan 29.

Abstract

Ceruloplasmin (Cp), an enzyme containing six copper atoms, has important roles in iron homeostasis and antioxidant defense. After spinal cord injury (SCI), the cellular components in the local microenvironment are very complex and include functional changes of resident cells and the infiltration of leukocytes. It has been confirmed that Cp is elevated primarily in astrocytes and to a lesser extent in macrophages following SCI in mice. However, its expression in other cell types is still not very clear. In this manuscript, we provide a sensible extension of these findings by examining this system within a female Sprague-Dawley rat model and expanding the scope of inquiry to include additional cell types. Quantitative reverse transcription polymerase chain reaction and Western blot analysis revealed that the Cp mRNA and protein in SCI tissue homogenates were quite consistent with prior publications. However, we observed that Cp was expressed not only in GFAP+ astrocytes (consistent with prior reports) but also in CD11b+ microglia, CNPase+ oligodendrocytes, NeuN+ neurons, CD45+ leukocytes, and CD68+ activated microglia/macrophages. Quantitative analysis proved that infiltrated leukocytes, activated microglia/macrophages, and astrocytes should be the major sources of increased Cp.

Keywords: astrocytes; ceruloplasmin; infiltrated leukocytes; microglia; spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',3'-Cyclic-Nucleotide Phosphodiesterases / metabolism
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Antigens, Nuclear / metabolism
  • Astrocytes / enzymology*
  • Astrocytes / pathology
  • CD11b Antigen / metabolism
  • Ceruloplasmin / biosynthesis*
  • Ceruloplasmin / metabolism
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Leukocyte Common Antigens / metabolism
  • Leukocytes / enzymology
  • Leukocytes / pathology
  • Macrophages / enzymology
  • Macrophages / pathology
  • Mice
  • Microglia / enzymology*
  • Microglia / pathology
  • Nerve Tissue Proteins / metabolism
  • Neurons / enzymology
  • Neurons / physiology
  • Oligodendroglia / enzymology
  • Oligodendroglia / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / chemically induced
  • Spinal Cord Injuries / pathology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antigens, Nuclear
  • CD11b Antigen
  • CD68 protein, rat
  • GFAP protein, rat
  • Glial Fibrillary Acidic Protein
  • Nerve Tissue Proteins
  • Rbfox3 protein, rat
  • Ceruloplasmin
  • Leukocyte Common Antigens
  • Ptprc protein, rat
  • 2',3'-Cyclic-Nucleotide Phosphodiesterases