Recombinant Human Granulocyte Colony-Stimulating Factor: Effects on Normal and Leukemic Myeloid Cells

Abstract

Experiments were conducted to isolate and characterize the gene and gene product of a human hematopoietic colony-stimulating factor with pluripotent biological activities. This factor has the ability to induce differentiation of a murine myelomonocytic leukemia cell line WEHI-3B(D+) and cells from patients with newly diagnosed acute nonlymphocytic leukemia (ANLL). A complementary DNA copy of the gene encoding a pluripotent human granulocyte colony-stimulating factor (hG-CSF) was cloned and expressed in Escherichia coli. The recombinant form of hG-CSF is capable of supporting neutrophil proliferation in a CFU-GM assay. In addition, recombinant hG-CSF can support early erythroid colonies and mixed colony formation. Competitive binding studies done with 125I-labeled hG-CSF and cell samples from two patients with newly diagnosed human leukemias as well as WEHI-3B(D+) cells showed that one of the human leukemias (ANLL, classified as M4) and the WEHI-3B(D+) cells have receptors for hG-CSF. Furthermore, the murine WEHI-3B(D+) cells and human leukemic cells classified as M2, M3, and M4 were induced by recombinant hG-CSF to undergo terminal differentiation to macrophages and granulocytes. The secreted form of the protein produced by the bladder carcinoma cell line 5637 was found to be O-glycosylated and to have a molecular weight of 19,600.

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1+ cells into the liver

“…Numerous cytokines such as GM-CSF, IL-3, IL-6, IL-11, and SCF promote granulopoiesis by themselves and/or in concert with G-CSF [9,10]. G-CSF is indispensable for both steady-state and emergency granulopoiesis [11][12][13][14], and IL-17 regulates G-CSF secretion [9,10,[15][16][17][18]. In addition to Gr-1 1 cells, g/d T cells also participate in early protection against L. monocytogenes infection [19][20][21][22].…”

“…GM-CSF plays a crucial role in emergency, but not in homeostatic, hematopoiesis and is required for effective hematopoiesis during immune activation [74]. In contrast, IL-17 promotes G-CSF secretion, which plays a central role in proliferation and differentiation of Gr-1 1 cells in both normal and inflammatory conditions [9][10][11][12][13][14][15][16][17][18]. Since these cytokines participate in early protection against L. monocytogenes infection [14, 74-76, 89, 90], it is feasible that iNKT cells are a major source of these cytokines in protection against L. monocytogenes infection.…”

Leukemic cells with 11q23 translocations express granulocyte colony-stimulating factor (G-CSF) receptor and their proliferation is stimulated with G-CSF

“…It has been well known that AML cells frequently express G-CSFR [28][29][30][31][32][33][34] and their proliferation are often stimulated with G-CSF. 30,32,33 In contrast, Mirro et al 35 reported that ALL cells rarely respond to cytokines including G-CSF.…”

Constitutive production of multiple cytokines and a human chorionic gonadotrophin beta-subunit by a human bladder cancer cell line (KU-19-19): possible demonstration of totipotential differentiation

“…In addition, a variety of non-haematopoietic malignant tumours, including bladder carcinoma (Welte et al, 1985a;Souza et al, 1986;Serve et al, 1991;Grammatico et al, 1993), have been confirmed to secrete G-CSF or GM-CSF (Wetzler et al, 1993) in amounts large enough to cause a significant systemic haematopoietic effect. Therefore, the leukaemoid reaction is a well-known paraneoplastic syndrome, which has been shown to arise from G-CSF and/or GM-CSF production by cancer cells (Wetzler et al, 1993).…”