Association between colony forming units-granulocyte macrophage expression of Ia-like (HLA-DR) antigen and control of granulocyte and macrophage production. A new role for prostaglandin E.

Abstract

A B S T R A C T The expression of Ia-like antigens on human colony forming units-granulocyte macrophage (CFU-GM) is related to S-phase of the cell cycle, and associated with the control of normal granulocyte and macrophage production by prostaglandin E and acidic isoferritins in vitro. Ia-antigen expression by CFU-GM is lost within 3-6 h of culture at 370C and occurs simultaneously with loss of responsiveness to inhibition by these factors. Culture of bone marrow CFU-GM in a limited exposure suspension culture with 1 AM-lpM prostaglandin E (PGE1 or PGE2), but not prostaglandin F2a or dibutyryl-cyclic-3'-5'-AMP results in the detection of CFU-GM Ia-antigen after 24 h. Antigen expression is associated with an absolute increase in total and S-phase CFU-GM, and restoration of responsiveness to inhibition by prostaglandin E and acidic isoferritins. The detection of Ia-antigen on CFU-GM after suspension culture with prostaglandin E results both from Iaantigen reexpression as well as stimulation of noncycling cells to enter S-phase, express Ia-antigen and give rise to CFU-GM sensitive to inhibition by prostaglandin E and acidic isoferritins. The sensitivity of CFU-GM to inhibition by these factors after suspension culture with prostaglandin E is identical to that of the same cells tested prior to the suspension culture. These studies provide evidence for a direct regulatory association between Ia-antigen expression and control of myeloid progenitor cell differentiation, and suggest a role for prostaglandin E in the control of CFU-GM cell cycle, Ia-antigen expression, and growth regulation.

Blockade of prostaglandin E2 signaling through EP1 and EP3 receptors attenuates Flt3L-dependent dendritic cell development from hematopoietic progenitor cells

“…In contrast to the effects of PGE 2 on myeloid, erythroid, and multipotential progenitor cell proliferation, [22][23][24][25]34 inhibition of PGE 2 biosynthesis did not affect BrdU incorporation in DC-committed progenitor cells, suggesting that PGE 2 does not primarily regulate DC-lineage progenitor cell proliferation. Because BrdU incorporation measures DNA replication not cell division, we confirmed this finding by in vitro CFDA staining that measures cell division.…”

“…Similar to that observed for steady state mice, blockade of PGE 2 synthesis during in vivo Flt3L treatment resulted in significantly reduced DC generation ( Figure 1D). Because DCs develop in the BM from DC lineage-committed HPCs 7,9,16 and we previously demonstrated that PGE 2 can differentially regulate HPCs depending on lineage, [21][22][23][24][25]34 we examined whether the attenuated development of DCs observed on inhibition of PGE 2 biosynthesis results from an effect on the DC-committed progenitor cell compartment. In mice treated with indomethacin for 6 days, the early BM common DC progenitors, CDP (Lin neg c-Kit int Flt3 ϩ CD115 ϩ ; Figure 1E), and immediate cDC precursors, pre-cDC (CD3/CD19/NK1.1/Ter119 neg CD11c ϩ MHCII Ϫ SIRP␣ int Flt3 ϩ ; Figure 1F), were significantly reduced compared with control.…”

Prostaglandin E2 enhances long-term repopulation but does not permanently alter inherent stem cell competitiveness

“…5 Using short-term ex vivo pulse exposure of bone marrow cells, similar to exposure strategies previously reported, 6,7 North and colleagues elegantly demonstrated that murine bone marrow transplantation was enhanced by dmPGE 2 . 5 We later demonstrated that this enhanced hematopoietic stem cell (HSC) engraftment resulted from an increase in CXCR4 on hematopoietic stem and progenitor cells and enhanced homing to the marrow; it also increased expression of Survivin, with reduced HSC apoptosis and increased HSC division.…”

Inhibitory effect of a human T cell hybrid factor on both cell growth and mixed lymphocyte reactivity. Correlation with class II molecule expression.

“…Inhibitory factors, most of which are leukocyte products, include lactoferrin (6), prostaglandin E (7), acidic isoferritin (8), and transferrin (9). In most of the feedback systems described, the Ia (class II) surface antigenic system appears to play a role in the proliferative events in the marrow (10)(11)(12). Both myeloid (colony-forming units granulocytic-monocytic [CFU-GM]) and erythroid progenitor cells (burst-forming units-erythroid and colony-forming units-erythroid [BFU-E and CFU-Ej) express Ta antigenic determinants on their surfaces, although these progenitor cells appear to be generated from pluripotent stem cells lacking Ta antigens (13,14).…”