Macrophages morphology and cytokine reeducation by ex situ copper thiol complexes

Immunopharmacol Immunotoxicol. 2024 Feb;46(1):20-32. doi: 10.1080/08923973.2023.2245559. Epub 2023 Aug 16.

Abstract

Objective: To study the reeducation effect of copper thiol complexes on macrophage morphology and cytokine expression.

Methods: The effect of copper thiol complexes was assessed on murine macrophages by the cell morphology observed through optical microscopy, while the expression of cytokines by protein abundance after stimulation. A viability experiment was performed on PMBC to confirm that copper complexes do not affect other cells.

Results: The M1 shape was reported after treatment with copper thiol complexes at 1-200 µM, while M2 behavior was documented between 50 and 800 µM. Surprisingly, a thin elongate morphology was observed between 400-800 µM like the M2 shape. The expression of M1 cytokines was noted ranging from 1 to 100 µM, with the highest yield at 1 µM (2243 pg/µL) for the copper-penicillamine complex. M2 production behavior was observed at 1-800 µM, with the highest abundance close to 1150 pg/µL (200-400 µM) was quantified from the copper-cysteine complex. Finally, LCCu complexes did not induce a cytotoxic response on PBMC while exhibiting a high IL-4 and IL-10 production, similar to their gold analogs.

Conclusions: The capacity of copper thiol complexes to reeducate M1 to M2 morphoexpression can be promising for cell protection by using copper thiol penicillamine or immuno-regeneration of tissues when using copper thiol cysteine.

Keywords: Reeducation; copper thiol complexes; cytokine expression; macrophages; morphology.

MeSH terms

  • Animals
  • Copper* / metabolism
  • Copper* / pharmacology
  • Cysteine / metabolism
  • Cysteine / pharmacology
  • Cytokines* / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Macrophages / metabolism
  • Mice
  • Penicillamine / metabolism
  • Penicillamine / pharmacology
  • Sulfhydryl Compounds / metabolism
  • Sulfhydryl Compounds / pharmacology

Substances

  • Cytokines
  • Copper
  • Sulfhydryl Compounds
  • Cysteine
  • Penicillamine