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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human granulocyte colony-stimulating factor (hG-CSF) specifically stimulates proliferation of neutrophils. Two crystal forms of a mutant of hG-CSF expressed in Escherichia coli have been obtained using the hanging drop vapour diffusion method. One form is triclinic, space group P1, with cell dimensions a = 37.3 A, b = 46.4 A, c = 47.7 A, alpha = 105.5 degrees, beta = 98.0 degrees and gamma = 109.4 degrees. The other is monoclinic, space group C2, with cell dimensions a = 82.0 A, b = 49.2 A, c = 49.4 A and beta = 113.9 degrees. Both crystal forms diffract beyond 2.0 A and are suitable for X-ray analysis.
J Mol Biol 1990 Jul 05
PMID:Crystallization and preliminary diffraction studies of recombinant human granulocyte-stimulating factor (KW2228). 169 50

32DC13(G) is an interleukin-3-dependent murine hematopoietic precursor cell line which differentiates into neutrophilic granulocytes upon exposure to granulocyte colony-stimulating factor (G-CSF) but ceases to proliferate and dies when exposed to granulocyte-macrophage (GM)-CSF. Surface receptors for GM-CSF are undetectable on 32DC13(G) cells but can be induced by priming the cells with G-CSF. Exposure of the G-CSF-primed cells to GM-CSF then results in the generation of monocytes as well as granulocytes. The acquired competence to respond to GM-CSF remains irreversibly encoded in the primed cells, although the GM-CSF receptor can be down regulated by interleukin-3. This phenomenon suggests a mechanism by which hematopoietic precursors may obtain additional receptors, thereby increasing their differentiative potential.
Mol Cell Biol 1990 Sep
PMID:Induction of the granulocyte-macrophage colony-stimulating factor (CSF) receptor by granulocyte CSF increases the differentiative options of a murine hematopoietic progenitor cell. 169 33

A number of investigators have demonstrated the association of CD5+ (Ly-1/Leu-1) B cells with autoimmunity, excessive B-cell proliferation, and transformation. Previous work from our laboratory, among others, suggests that the selective advantage of this frequently autoreactive B-cell subset is to provide activation signals to conventional antigen-specific B cells. If one current hypothesis is correct then the overrepresentation of CD5+ B cells in some diseases and their novel capacity to act as helper cells reflect the activities of a separate B-cell lineage. Because of these observations it is of particular interest to evaluate the factors which contribute to the maturation of the CD5+ B-cell subset. The possibility that CD5+ B cells produce a factor or factors capable of influencing their own development was the focus of the present investigation. Rather than attempt to obtain soluble factors from heterogeneous CD5+ B-cell populations which could be contaminated with cytokine secreting monocytes or which could require as yet undefined activation signals in order to secrete putative factors, we chose to evaluate the production of CD5+ B-cell inducing factor(s) by monoclonal CD5+ B-cell hybridomas. Added incentive to this approach was provided by the observation that these hybridomas elaborate a factor(s) which, together with (NPb) idiotype-specific antibody produced by the hybridoma, substitutes for CD5+ B-cell populations in activating antigen-specific (NPb idiotypic) B cells in vitro. Furthermore, because of the low percentage of CD5+ B cells in the spleen and their relatively low level of CD5 antigen expression, we employed a sensitive functional assay rather than surface antigen expression alone to detect small numbers of mature CD5+ B helper cells. With this previously described system it was possible to observe the induction of functional CD5+ B cells following a 40 h culture of apparently CD5- B-cell populations with a 19-22 kd factor or factors derived from a CD5+ B hybridoma. Data presented here and elsewhere suggest that this CD5+ B-cell inducing activity is not mediated by IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IFN-gamma, GM-CSF, or TNF. The role that such a B cell derived, B-cell directed factor may play in immunity and disease is discussed.
J Mol Cell Immunol 1990
PMID:A CD5+ B cell hybridoma derived factor(s), which induces maturation of CD5+, idiotype-specific B-cell populations. 169 80

The tyrosine kinase domains of the platelet-derived growth factor (PDGF) and colony-stimulating factor-1 (CSF-1)/c-fms receptors are interrupted by kinase inserts (ki) which vary in length and amino acid sequence. To define the role of the ki in the human alpha PDGF receptor (alpha PDGFR), we generated deletion mutants, designated alpha R delta ki-1 and alpha R delta ki-2, which lacked 80 (710 to 789) and 95 (695 to 789) amino acids of the 104-amino-acid ki region, respectively. Their functional characteristics were compared with those of the wild-type alpha PDGFR following introduction into a naive hematopoietic cell line, 32D. Biochemical responses, including PDGF-stimulated PDGFR tyrosine phosphorylation, phosphatidylinositol (PI) turnover, and receptor-associated PI-3 kinase activity, were differentially impaired by the deletions. Despite a lack of any detectable receptor-associated PI-3 kinase activity, 32D cells expressing alpha R delta ki-1 showed only partially impaired chemotactic and mitogenic responses and were capable of sustained proliferation in vitro and in vivo under conditions of autocrine stimulation by the c-sis product. 32D transfectants expressing the larger ki deletion (alpha R delta ki-2) showed markedly decreased or abolished biochemical and biological responses. However, insertion of the highly unrelated smaller c-fms (685 to 750) ki domain into alpha R delta ki-2 restored each of these activities to wild-type alpha PDGFR levels. Since the CSF-1R does not normally induce PI turnover, the ability of the c-fms ki domain to reconstitute PI turnover in the alpha R delta ki-2 transfectant provides evidence that the ki domain of the alpha PDGFR does not directly couple with this pathway. Taken together, all od these bindings imply that their ki domains have evolved to play very similar roles in the known signaling functions PDGF and CSF-1 receptors.
Mol Cell Biol 1991 Jan
PMID:Deletion or substitution within the alpha platelet-derived growth factor receptor kinase insert domain: effects on functional coupling with intracellular signaling pathways. 170 11

We have established primary lines of fibroblasts from nasal polyp (NP) tissues as well as from normal nasal (NN) mucosa and have examined the ability of these cells to release hormone-like peptide messenger molecules (cytokines). Our results show that human upper airway fibroblasts release granulocyte/macrophage colony-stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), and macrophage-CSF (M-CSF) in vitro. We also show that fibroblasts derived from NP tissue express the gene for GM-CSF at a higher level, and release the GM-CSF product in greater amounts, than NN fibroblasts. In addition, we have examined the ability of these fibroblasts and their conditioned medium (CM) to induce differentiation of human hemopoietic progenitor cells. After 7 d, cultures of these cells in RPMI-10% fetal bovine serum contained 5 +/- 2.5% (mean +/- SD) neutrophils. In contrast, culture of progenitor cells with fibroblasts resulted in significantly greater neutrophilic differentiation (18 +/- 4%). Culture in fibroblast-CM induced a similar degree of differentiation, and fibroblast-CM from NP fibroblasts elicited greater differentiation compared to CM from NN fibroblasts (17.5 +/- 3 versus 12 +/- 3%). The neutrophilic differentiation induced by fibroblast-CM can be fully inhibited by preincubating this CM with a monoclonal neutralizing antibody to human GM-CSF. Thus, our results demonstrate: (1) the ability of human upper airway fibroblasts to release GM-, G-, and M-CSF in vitro; (2) that fibroblasts derived from NP tissues express the gene and release the product GM-CSF at greater levels compared to NN fibroblasts; and (3) that fibroblast-derived GM-CSF causes neutrophilic differentiation of human hemopoietic progenitors.
Am J Respir Cell Mol Biol 1991 Jan
PMID:Neutrophilic differentiation induced by human upper airway fibroblast-derived granulocyte/macrophage colony-stimulating factor (GM-CSF). 170 52

We examined the ability of conditioned medium (CM) generated by human upper airway epithelial (Ep) cells from normal (NN) and inflamed, allergic rhinitis (AR) and nasal polyp (NP) tissues to induce monocytic differentiation of hemopoietic progenitors of the HL-60 myeloid leukemia cell line in vitro. In HL-60 cells cultured in RPMI with 10% FBS, there was differentiation to 0.4 +/- 0.4% monocytic cells. NN-, AR-, and NP-EpCM induced differentiation to 23 +/- 6%, 42 +/- 11%, and 71 +/- 10% monocytic cells, respectively. EpCM also induced isolated peripheral blood nonadherent mononuclear cells to express monocyte/macrophage-specific antigens as detected by immunohistochemistry using FMC-32 monoclonal antibodies (anti-CD14). We also examined the cytokine content of these EpCMs and found that they contained granulocyte/macrophage colony-stimulating factor (GM-CSF): 126 +/- 35, 198 +/- 22, and 489 +/- 118 pg/ml for NN-, AR-, and NP-EpCM, respectively. These CMs also contained granulocyte-CSF (G-CSF) and interleukin-6 (IL-6), but there were no significant differences between normal and inflamed tissue-derived cell supernatants. No macrophage-CSF (M-CSF) was detected in these EpCMs. Recombinant human GM-CSF, G-CSF, and IL-6, alone and in combinations, at doses similar to or greater than those found in the EpCMs, did not induce comparable monocytic differentiation of HL-60 cells. Preincubation of the EpCM with neutralizing anti-GM-CSF, anti-G-CSF, or anti-IL-6 antibodies did not significantly inhibit the monocytic differentiation induced by the EpCM.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Mar
PMID:Monocyte-macrophage differentiation induced by human upper airway epithelial cells. 170 10

A peptide antiserum (anti-A) directed to the intracellular, juxtamembrane region (residues 552 to 574) of the human colony-stimulating factor 1 receptor (CSF-1R) precipitated only ligand-activated, native receptors from solution but bound to unstimulated forms after their denaturation. Two peptide antisera (anti-KI1 and -KI2), directed to residues 679 to 700 and 701 to 721, respectively, in the CSF-1R kinase insert (KI) domain and including mapped sites of ligand-induced phosphorylation at Tyr-699 and Tyr-708, bound at least 80% of the receptor molecules expressed in either CSF-1-stimulated or unstimulated cells. Immune complexes formed with anti-KI1, anti-A, or a peptide antiserum to the CSF-1R carboxyl terminus (anti-C-ter) coprecipitated CSF-1R complexed to a phosphatidylinositol 3-kinase (PtdIns 3-K) from CSF-1-stimulated cells, whereas anti-KI2 serum did not. In an in vitro assay, binding of CSF-1R to PtdIns 3-K required receptor tyrosine phosphorylation but not CSF-1R-mediated phosphorylation of the lipid kinase, and the association was specifically blocked by anti-KI2 or antibodies to phosphotyrosine. Neither anti-KI1, anti-A, nor anti-C-ter serum inhibited binding. We conclude that (i) only a minority of ligand-activated receptors form a stable complex with PtdIns 3-K in vivo, (ii) efficient binding of the lipid kinase requires receptor tyrosine phosphorylation within the CSF-1R KI domain, and (iii) a region within the KI domain defined by residues 701 to 721 at least partially overlaps the PtdIns 3-K binding site.
Mol Cell Biol 1991 May
PMID:Peptide antisera to human colony-stimulating factor 1 receptor detect ligand-induced conformational changes and a binding site for phosphatidylinositol 3-kinase. 170 91

One of the hallmarks of the granulomatous response to infection is the formation of multinucleated giant cells (MGC.) In an effort to study MGC, we examined the fusion-promoting effects of a variety of stimulating factors on human peripheral blood monocytes cultured on plastic surfaces in serum-supplemented media. MGC formation was minimally to moderately enhanced by interferon-gamma (IFN-gamma), interleukin (IL)-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), retinoic acid (RA), and IL-6. IL-4 (which has been reported to promote MGC formation from murine macrophages) had an inhibitory effect. IFN-gamma was not required for MGC formation but it significantly increased the fusion-promoting activity of GM-CSF, 1,25-(OH)2D3, RA, and IL-6, IL-3, a hematopoietic growth factor, has been recently shown to induce osteoclast formation from murine bone marrow mononuclear cells. The most striking effect was seen with the combination of IL-3 and IFN-gamma. Fusion index is defined as a percentage of nuclei found within MGC, and an index of 67% at 1 wk was found. The formation of some very large cells with 50 to 100 nuclei was noted. Both Langhans' and foreign-body type cells were seen. Transmission electron micrographs clearly demonstrate the absence of plasma membrane between nuclei. Induction of MGC from peripheral human blood monocytes by IL-3 and IFN-gamma provides an in vitro system for the study of the formation and function of these cells.
Am J Respir Cell Mol Biol 1992 Jan
PMID:Induction of multinucleated giant cell formation from in vitro culture of human monocytes with interleukin-3 and interferon-gamma: comparison with other stimulating factors. 172 95

Colony-stimulating factor-1 (CSF-1) has been primarily characterized as a hematopoietic growth factor required for the proliferation and differentiation of monocytic cells. Recent immunohistological observations have shown that this growth factor is also synthesized by the glandular epithelial cells of the pregnant human endometrium and by first trimester human trophoblasts. In the present study endometrial glands were purified from nonpregnant human endometria collected through the menstrual cycle and examined for CSF-1 mRNA expression. The two major mRNAs (4.0 and 3.0 kilobases in length) detected in midproliferative and midsecretory phases differed in the size of the exon 6 and coded, respectively, for a secreted and a cell surface form of CSF-1. The 3.0-kilobase transcript represented a novel CSF-1 mRNA species that was molecularly cloned and sequenced. These data raise the possibility that CSF-1 may be involved in both distant and cell to cell regulatory pathways of cell proliferation and differentiation in the human endometrium.
Mol Endocrinol 1991 Dec
PMID:Expression of colony-stimulating factor-1 (CSF-1) messenger RNA in human endometrial glands during the menstrual cycle: molecular cloning of a novel transcript that predicts a cell surface form of CSF-1. 179 39

Cultured human bronchial epithelial cells constitutively produce granulocyte/macrophage colony-stimulating factor (GM-CSF). An upregulation of the synthesis and release of GM-CSF from those cells might contribute to the persistence of infiltration and local activation of inflammatory cells in some inflammatory diseases of the airways, such as asthma. Increased levels of immunoreactive and biologically active interleukin-1 (IL-1) have been identified in the airway secretions of asthmatic patients, together with an increase in GM-CSF contents. As IL-1 is known to upregulate GM-CSF production in many cell populations, in this study we investigated the ability of IL-1 to bind to specific receptors on bronchial epithelial cells and promote GM-CSF synthesis and release. Bronchial epithelial cells possessed specific single-class surface receptors for recombinant IL-1. The addition of exogenous IL-1 led to a dose-dependent increase in the accumulation of GM-CSF mRNA and release of immunoreactive GM-CSF to the culture medium. Release of IL-1 in the bronchial mucosa during allergic and nonallergic responses may lead to enhanced GM-CSF synthesis and release by epithelial cells, thus promoting airway inflammation.
Am J Respir Cell Mol Biol 1991 Jun
PMID:Interleukin-1 binds to specific receptors on human bronchial epithelial cells and upregulates granulocyte/macrophage colony-stimulating factor synthesis and release. 182 52


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