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Blood, Vol. 94 No. 4 (August 15), 1999:
pp. 1359-1371
Calcium Ionophore-Treated Myeloid Cells Acquire Many Dendritic Cell
Characteristics Independent of Prior Differentiation State,
Transformation Status, or Sensitivity to Biologic Agents
Gary K. Koski,
Gretchen N. Schwartz,
David E. Weng,
Ronald E. Gress,
Friederike H.C. Engels,
Maria Tsokos,
Brian J. Czerniecki, and
Peter A. Cohen
From the Medicine Branch, National Cancer Institute, Laboratory of
Pathology, National Cancer Institute, Bethesda, MD; and the Department
of Surgery, University of Pennsylvania Medical Center, Philadelphia,
PA.
We previously reported that treatment of human peripheral blood
monocytes or dendritic cells (DC) with calcium ionophore (CI) led to
the rapid (18 hour) acquisition of many characteristics of mature DC,
including CD83 expression. We therefore investigated whether
less-mature myeloid cells were similarly susceptible to rapid CI
activation. Although the promyelocytic leukemia line HL-60 was
refractory to cytokine differentiation, CI treatment induced
near-uniform overnight expression of CD83, CD80 (B7.1), and CD86
(B7.2), as well as additional characteristics of mature DC. Several
cytokines that alone had restricted impact on HL-60 could enhance
CI-induced differentiation and resultant T-cell sensitizing capacity.
In parallel studies, CD34pos cells cultured from normal
donor bone marrow developed marked DC-like morphology after overnight
treatment with either rhCD40L or CI, but only CI simultaneously induced
upregulation of CD83, CD80, and CD86. This contrasted to peripheral
blood monocytes, in which such upregulation could be induced with
either CI or rhCD40L treatment. We conclude that normal and transformed
myeloid cells at many stages of ontogeny possess the capacity to
rapidly acquire many properties of mature DC in response to CI
treatment. This apparent ability to respond to calcium mobilization,
even when putative signal-transducing agents are inoperative, suggests strategies for implementing host antileukemic immune responses.
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