International Journal of Hematology

DOI: 10.1532/IJH97.NA0405 Pages: 131-137

Protein Kinase C Blockade Inhibits Differentiation of Myeloid Blasts into Dendritic Cells by Calcium Ionophore A23187

1. University of Oklahoma Health Sciences Center and OU Cancer Center, Section of Hematology-Oncology

2. University of Oklahoma Health Sciences Center, Department of Medicine

3. University of Miami, Division of Hematology-Oncology and Department of Microbiology and Immunology

Correspondence to:
Mohamed A. Kharfan-Dabajaa
Tel: 1-405-270-1565
Fax: 1-405-270-1569
Email: Mohamed-Kharfandabaja@ouhsc.edu

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Abstract

Direct differentiation of myeloid leukemia blasts into antigen-presenting dendritic cells (DCs) for use as cellular vaccines is unique in that identification of tumor-specific antigens may not be necessary because the antigens should already be endogenously expressed.We hypothesized that signaling through protein kinase C (PKC) is required for differentiation of HL-60 promyeloblasts into DCs upon stimulation with calcium ionophore A23187. To demonstrate the inhibitory effect of PKC blockade, we pretreated HL-60 myeloid blasts with the protein kinase inhibitor bisindolylmaleimide I (Bis-1) for 24 hours and then treated the cells with calcium ionophore A23187 for an additional 24 hours. Controls consisted of HL-60 blasts treated with A23187, Bis-1 alone, or media.We noted that blasts cultured in media, Bis-1, or Bis-1 then A23187 did not develop the morphologic and phenotypic DC characteristics, up-regulate Rel B, or activate allogeneic T-cells. Our findings suggested that PKC blockade inhibits morphologic, phenotypic, and functional differentiation of HL-60 promyeloblasts into antigen-presenting DCs. Our findings supported the role of PKC as an obligatory pathway for calcium ionophore A23187-induced differentiation of HL-60 myeloblasts into antigen-presenting DCs.

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