Ascorbic Acid Modulates Cell Migration in Differentiated HL-60 Cells and Peripheral Blood Leukocytes

Mol Nutr Food Res. 2015 Aug;59(8):1513-23. doi: 10.1002/mnfr.201400893. Epub 2015 May 8.

Abstract

Scope: The impact of L-ascorbic acid (L-AA) on the chemokinesis (CK) and chemotaxis (CT) of HL-60 cells and polymorphonuclear cells (PMN) was investigated.

Methods and results: HL-60 cells were differentiated with DMSO, retinoic acid (RA), vitamin D, or L-AA. Chemokinesis and chemotaxis of differentiated HL-cells were assayed. Vitamin D3-treated HL-60 cells (dHL-60vitD3 cells) and RA-treated cells (dHL-60RA cells) acquired monocyte/macrophage-like and neutrophil-like phenotypes, respectively. DMSO induced the differentiation of an intermediate phenotype (dHL-60DMSO cells), whereas L-AA downregulated neutrophil markers (dHL-60L-AA cells). dHL-60DMSO cells had increased CK and potent CT in gradients of IL-8 and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). dHL-60RA cells and dHL-60L-AA cells migrated less toward IL-8 and fMLP; dHL-60vitD3 cells preferably responded to fMLP. L-AA enhanced CK of dHL-60DMSO cells and was a weak chemo-attractant. In human leukocytes, IL-8 and fMLP triggered receptor-mediated chemotaxis. CXCR2 and fMLPR were downregulated by IL-8 and fMLP, respectively. L-AA stimulated chemotaxis although significantly less than IL-8 and fMLP. IL-8 targeted chemotaxis was enhanced both in HL-60 cells and leukocytes when cells were incubated with L-AA.

Conclusion: L-AA modulated chemokinesis and had significant chemo-attractant properties, which were independent on fMLP or IL-8 receptors. The results suggest that L-AA improves leukocyte function in innate immune responses.

Keywords: Chemotaxis; Innate immune response; L-ascorbic acid; Leukocytes.

Publication types

  • Comparative Study

MeSH terms

  • Antigens, CD / metabolism
  • Ascorbic Acid / metabolism*
  • Biomarkers / metabolism
  • Calcifediol / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cell Movement / drug effects
  • Cells, Cultured
  • Chemotaxis, Leukocyte* / drug effects
  • Dimethyl Sulfoxide / pharmacology
  • HL-60 Cells
  • Humans
  • Immunity, Innate* / drug effects
  • Interleukin-8 / metabolism
  • Leukocytes / cytology
  • Leukocytes / drug effects
  • Leukocytes / immunology
  • Leukocytes / metabolism*
  • Leukopoiesis* / drug effects
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism*
  • N-Formylmethionine Leucyl-Phenylalanine / metabolism
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Receptors, Interleukin-8B / agonists
  • Receptors, Interleukin-8B / metabolism
  • Solvents / pharmacology
  • Tretinoin / metabolism

Substances

  • Antigens, CD
  • Biomarkers
  • CD66 antigens
  • Cell Adhesion Molecules
  • Interleukin-8
  • Receptors, Interleukin-8B
  • Solvents
  • Tretinoin
  • N-Formylmethionine Leucyl-Phenylalanine
  • Calcifediol
  • Ascorbic Acid
  • Dimethyl Sulfoxide