Calcium ionophore-treated myeloid cells acquire many dendritic cell characteristics independent of prior differentiation state, transformation status, or sensitivity to biologic agents.
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, CD34(pos) 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.
Koski
G K
GK
Medicine Branch, National Cancer Institute, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Schwartz
G N
GN
Weng
D E
DE
Gress
R E
RE
Engels
F H
FH
Tsokos
M
M
Czerniecki
B J
BJ
Cohen
P A
PA
D015703:Antigens, CD / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen; D000001:Calcimycin / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology; D018922:HL-60 Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology; D007476:Ionophores / Q000494:pharmacology*; D019891:Leukopoiesis / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D000001:Calcimycin; D007136:Immunoglobulins; D007476:Ionophores; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C497964:CD86 protein, human