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Expression and function of the human granulocyte-macrophage colony- stimulating factor receptor alpha subunit 总被引:2,自引:0,他引:2
To determine the expression and function of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha chain (GMR alpha) during hematopoiesis and on leukemic cells, monoclonal antibodies were raised by immunizing mice with cells expressing high levels of human GMR alpha. A pool of five antibodies isolated from three different mice was used to characterize GMR alpha. This antibody pool (anti-GMR alpha) immunoprecipitated a protein with the expected molecular weight of GMR alpha from COS cells transiently transfected with the GMR alpha gene. In factor-dependent cells, GMR alpha existed as a phosphoprotein. However, its phosphorylation was not stimulated by the presence of GM- CSF. Anti-GMR alpha inhibited the GM-CSF-dependent growth of cell lines and normal bone marrow cells and inhibited the binding of iodinated GM- CSF to its receptor. Cell surface expression of GMR alpha was examined using anti-GMR alpha and flow cytometry. GMR alpha was readily detectable on both blood monocytes and neutrophils. In adherence- depleted normal bone marrow, two separate populations expressed GMR alpha. The most positive cells were predominantly macrophages, whereas the cells that expressed less GMR alpha were largely myelocytes and metamyelocytes. A small population of lin-CD34+ or CD34+CD38- cells also expressed GMR alpha, but they were not capable of significant growth in colony-forming assays. In contrast, the majority of lin-CD34+ and CD34+CD38- cells were GMR alpha-, yet they produced large numbers of myeloid and erythroid colonies in the same assay. Malignant cells from patients with leukemia were also tested for GMR alpha expression. All of the myeloid leukemias and only rare lymphoid leukemias surveyed tested positive for GMR alpha. These results show that anti-GMR alpha is useful for the functional characterization of the GMR alpha and for the detection of myeloid leukemia and that GMR alpha is expressed on certain lineages throughout hematopoietic development; however, progenitors that express the receptor may have a reduced capacity to proliferate in response to hematopoietic growth factors. 相似文献
596.
Chan TM; Wu PC; Lau JY; Lok AS; Lai CL; Cheng IK 《Nephrology, dialysis, transplantation》1997,12(7):1414-1419
BACKGROUND: This study examined the efficacy and tolerability of interferon
alpha-2b (IFN) in the treatment of chronic hepatitis C virus (HCV)
infection in patients on maintenance haemodialysis. METHODS: A 24- month
prospective cohort study was performed in 11 HCV RNA-positive haemodialysis
patients, who were treated with IFN at 3 MU thrice weekly for 6 months.
Serial biochemical and virological monitors included serum alanine
aminotransferase levels, and HCV RNA by both qualitative PCR assay and
quantitative bDNA assay. HCV genotypes were determined by PCR and
nucleotide sequencing. Ten patients had baseline liver biopsy. RESULTS: HCV
genotypes 1b and 2b were identified in 10 and one patients respectively.
Six (55%) patients had biochemical and/or histological features of chronic
active hepatitis before treatment. All 11 patients became HCV RNA-negative
by PCR, with normalization of deranged aminotransferase levels, within 2-8
weeks of IFN therapy. HCV RNA reappeared in eight (73%) patients 2-8 weeks
after the cessation of IFN, while biochemical relapse occurred in six (55%)
patients. Sustained eradication of HCV was achieved in three (27%)
patients. Sustained responders were characterized by pretreatment HCV RNA
level < 3.5 x 10(5) Eq/ml as determined by the bDNA assay, and less
severe histological abnormalities ('Total score' 1.7 +/- 1.2 compared to
5.4 +/- 2.2 in relapsers, P < 0.05). HCV RNA levels were similar before
and after IFN treatment in non-responders and relapsers. Persistent malaise
and poor appetite were noted in eight (73%) patients during IFN therapy.
Other side-effects of IFN included the exacerbation of anaemia, induction
of resistance to erythropoietin, weight loss, and reduced serum albumin
level. CONCLUSIONS: Eradication of chronic HCV infection with IFN can be
achieved in 27% of haemodialysis patients. Predictors of sustained response
include low baseline HCV RNA level and mild liver pathology. Virological
relapse can occur despite normal liver biochemistry. Exacerbation of
anaemia, erythropoietin resistance, and malnutrition constitute the
side-effects of IFN that deserve special attention in uraemic subjects.
相似文献
597.
Human bone marrow microvascular endothelial cells support long-term proliferation and differentiation of myeloid and megakaryocytic progenitors 总被引:31,自引:9,他引:22
Rafii S; Shapiro F; Pettengell R; Ferris B; Nachman RL; Moore MA; Asch AS 《Blood》1995,86(9):3353-3363
Endothelial cells are a major component of the bone marrow (BM) microenvironment that regulate the trafficking and homing of hematopoietic progenitor and stem cells. In this paper, we provide evidence that BM endothelial cells (BMECs) also support multilineage hematopoiesis by elaboration of soluble cytokines. Hematopoietic progenitor cells incubated in direct contact with BMEC monolayers, or physically separated by microporous membrane, expanded five-fold to sevenfold at 7 days, in the absence of exogenous cytokines. Flow cytometric analysis of proliferating progenitor cells grown in the presence of BMEC monolayers showed that by day 14 of coculture, 70% to 80% of hematopoietic cells were myeloid, expressing CD15 or CD14, and 14% to 19% were megakaryocytic, expressing GPIIb/IIIa or GPIb. CD34+ cells derived from umbilical cord blood, cultured in the upper chamber of transwell culture plates, as well as the cells grown in direct contact with BMEC monolayers, generated progenitors for up to 70 days. Unstimulated BMEC monolayers constitutively produce interleukin-6, Kit- ligand, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor. These data suggest that BMEC regulate proliferation of hematopoietic progenitor cells and long-term culture initiating cells by elaboration of lineage-specific cytokines. 相似文献
598.
Routine helical CT of the abdomen: image quality considerations 总被引:1,自引:0,他引:1
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