Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on canine hematopoiesis was evaluated. rhGM-CSF stimulated granulocyte-macrophage colony formation of canine marrow depleted of accessory cells up to tenfold. Stimulation of colony formation was abrogated by anti-rhGM-CSF antiserum or heat inactivation. rhGM-CSF also stimulated in vivo canine hematopoiesis both when given as continuous i.v. infusion and as intermittent s.c. injections. Neutrophil, monocyte, and lymphocyte counts were increased three- to eightfold above controls, whereas values for eosinophils, reticulocytes, and hematocrits were not changed. Bone marrow histology after 2 weeks of treatment with rhGM-CSF showed hypercellularity with myeloid hyperplasia and left-shifted granulocytopoiesis. After discontinuation of rhGM-CSF, peripheral leukocyte counts returned to control level within 3-7 days. Platelet counts decreased rapidly after starting rhGM-CSF, to 5000-15,000 platelets/mm3, and increased within 24 h after stopping rhGM-CSF treatment, whereas marrow histology after 2 weeks of rhGM-CSF application showed the normal number and morphology of megakaryocytes.
Exp Hematol 1989 Sep
PMID:Stimulation of canine hematopoiesis by recombinant human granulocyte-macrophage colony-stimulating factor. 267 May 96

Solid tumor biopsies from 33 patients were tested in vitro to evaluate the growth modulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). In 29 of 33 studies (88%), addition of GM-CSF either had no effect on in vitro growth, or induced growth inhibition. While significant growth inhibition was observed in 10 studies, marked inhibition was only observed in three studies. However, all dose-response curves were usually flat, suggesting indirect effects. Moderate growth stimulation was observed in four instances, which may have been due to residual granulocyte-macrophage progenitors within the biopsies. We conclude that GM-CSF has little or no growth-modulatory effect on most nonhematopoietic neoplasms. The primary role of GM-CSF in patients with solid tumors appears to be in prevention or reversal of myelosuppression associated with therapy. Thus, while GM-CSF seems unlikely to have a role in monotherapy of cancer, it is also unlikely to have its utility compromised by enhancement of tumor growth.
J Clin Oncol 1989 Sep
PMID:Effects of granulocyte-macrophage colony-stimulating factor on in vitro growth of human solid tumors. 267 Dec 90

Induction of differentiation in one type of clone of mouse myeloid leukemic cells by mouse or human interleukin 6 (IL-6) and in another type of clone by mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) was found to be associated with induction of IL-6 and GM-CSF mRNA and protein. The results indicated that IL-6 and GM-CSF could positively autoregulate their own gene expression during myeloid cell differentiation. It is suggested that this autoregulation may serve to enhance and prolong the signal induced by these proteins in cells transiently exposed to IL-6 or GM-CSF.
Mol Cell Biol 1989 Sep
PMID:Autoregulation of interleukin 6 and granulocyte-macrophage colony-stimulating factor in the differentiation of myeloid leukemic cells. 267 90

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was found to increase the adherence of purified peripheral blood monocytes to plastic surfaces and to monolayers of human umbilical vein endothelial cells. With plastic surfaces as a model 9-hr culture with GM-CSF was necessary for enhancement, and maximum levels were obtained after 24-hr stimulation. GM-CSF-stimulated adherence must require new RNA and protein synthesis because actinomycin D and cycloheximide abolished existing adherence and prevented further monocyte attachment. Interestingly, shorter incubations (1-2 hr) with cycloheximide increased adherence, suggesting a labile inhibitor. Formaldehyde fixation of monocytes but not of human vein endothelial cells abolished adherence, indicating the need for actively metabolizing monocytes. Thus, a hemopoietic growth factor, responsible for the proliferation and differentiation of monocytes, can also alter their adhesive characteristics. These observations may have important implications in pathological situations and in the in vivo use of GM-CSF.
Proc Natl Acad Sci U S A 1989 Sep
PMID:Regulation of human monocyte adherence by granulocyte-macrophage colony-stimulating factor. 267 50

Presented are the steps in creating a recombinant DNA molecule, examples of recombinant drug products, a description of DNA fingerprinting methods for diagnosing diseases, a discussion of the patenting of recombinant drugs, and a look to the future of this revolutionary biotechnology. Constructing a recombinant DNA molecule involves cutting the DNA into fragments with restriction endonucleases and rejoining the fragments in novel arrangements with ligase. Propagating the molecule in a microorganism, or cloning, is necessary to increase the number of gene copies to facilitate detection of the gene of interest and to produce the protein it encodes. Recombinant DNA drug products have been developed that represent the communicator, structural, and modifier classes of proteins. Recombinant communicator proteins include interferons alfa-2a and alfa-2b and granulocyte-macrophage colony-stimulating factor (immune system modulators); epidermal growth factor and erythropoietin (tissue repair promoters); and human insulin, growth hormone, and atrial peptide (metabolism modulators). Recombinant structural proteins include hepatitis B virus vaccine and CD4 protein, and recombinant modifier proteins include tissue plasminogen activator and superoxide dismutase (agents that split or splice organic molecules). In the future, gene defects associated with genetic diseases will be unraveled, leading to the production of new therapeutic agents designed to counteract or actually reverse those defects. Recombinant protein drugs will be further tailored to enhance their activity and specificity. These advances are so novel and momentous that patent protection has been extended not only to recombinant drugs but to the recombinant microorganisms in which they are manufactured. In cloning genes, investigators directly use the protein designs that occur naturally. Basic research will soon lead to the engineering of novel proteins with specified functions.
Am J Hosp Pharm 1989 Sep
PMID:Drug products of recombinant DNA technology. 267 63

Lymph-borne dendritic cells (L-DC) collected from the thoracic duct of rats following mesenteric lymphadenectomy are derived from the small intestine. We have cultured these cells in vitro and examined their survival and phenotypic and functional changes. L-DC survive poorly in culture in normal media (less than 50% overnight) but survival can be markedly increased by supplementation with Con A-stimulated spleen cell supernatant or recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) but not by recombinant IL-1, IL-2, IFN-gamma or by an IL-3-rich supernatant. The effects of GM-CSF are blocked by a specific antiserum. L-DC display heterogeneity for some surface markers, cytoplasmic inclusions and enzyme reactivity. After 16-48 hr culture the pattern of expression is markedly different. The numbers of Thy-1-positive L-DC and the amount of Thy-1 expressed increases, as do the numbers of L-DC expressing OX48 antigen. All L-DC remain Ia positive, but the proportion expressing the iC'3b receptor, non-specific esterase or cytoplasmic DNA inclusions decreases to almost zero. In contrast to Langerhans' cells, fresh L-DC are potent stimulators of an allogeneic mixed leucocyte reaction (MLR) but their potency is considerably increased after 16 hr culture. Also in contrast to Langerhans' cells, the increase in potency is not affected by culture with CAS and is thus unlikely to be dependent on GM-CSF. The changes described in L-DC properties could be related to their role as antigen-presenting cells.
Immunology 1989 Sep
PMID:Properties of lymph-borne (veiled) dendritic cells in culture. I. Modulation of phenotype, survival and function: partial dependence on GM-CSF. 268 Sep 6

Fresh lymph-borne (veiled) dendritic cells (L-DC) in the rat are almost totally negative for the interleukin-2 (IL-2) receptor detected by the monoclonal antibody (mAb) MRC OX39. After 16 hr culture more than 90% of L-DC are OX39 positive, and increased levels of expression can be seen within 5 hr culture. In cultures of L-DC and allogeneic lymphocytes. L-DC appear to express the IL-2 receptor more rapidly than lymphocytes. The intensity of labelling of L-DC is variable but maximal levels are similar to those seen on lymphoblasts. Culture in the presence of concanavalin A (Con A)-stimulated spleen cell supernatants or recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) results in a more rapid and intense expression of the IL-2 receptor by L-DC. L-DC cultured following rigorous T-cell depletion, or derived from athymic rats also express the IL-2 receptor after culture with GM-CSF. Cultured, but not fresh, L-DC bind iodinated recombinant IL-2 in a dose-dependent manner and binding is inhibited by excess unlabelled ligand. The amount of IL-2 bound varies but maximal amounts are similar to those bound by lymphoblasts. Following intravenous endotoxin injection, a large proportion of freshly collected L-DC express the IL-2 receptor and the number of L-DC released into the lymph is increased. An antibody to the IL-2 receptor which blocks an allogeneic MLR has no effect on a xenogeneic MLR using rat L-DC as stimulators and mouse lymphocytes as responders.
Immunology 1989 Sep
PMID:Properties of lymph-borne (veiled) dendritic cells in culture. II. Expression of the IL-2 receptor: role of GM-CSF. 268 Sep 7

The activity of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) for increasing leukocyte production and enhancing mature neutrophil function has been clearly demonstrated in phase I clinical trials in patients with a variety of hematologic and malignant diseases. The focus of current studies includes determination of optimal administration schedules and its use in combination with myelosuppressive chemotherapy, radiation therapy or antimicrobial agents. The utility of GM-CSF as a stimulant of host defense against infections and tumors is also under study.
Hematol Oncol Clin North Am 1989 Sep
PMID:Clinical role of granulocyte-macrophage colony-stimulating factor. 269 75

Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5) are T lymphocyte-derived glycoproteins that stimulate the development of eosinophils from bone marrow precursors. These eosinophil hemopoietins also regulate functions of mature eosinophils, enhancing their ability to infiltrate tissues and to secrete biologically active substances at the tissue site. In these ways, the eosinophil hemopoietins have a major impact on the development of eosinophilia-associated disease.
Hematol Oncol Clin North Am 1989 Sep
PMID:Hemopoietins for eosinophils. Glycoprotein hormones that regulate the development of inflammation in eosinophilia-associated disease. 269 80

The histamine-producing cell-stimulating factor (HCSF) was first described as a lymphokine which is produced during secondary mixed leukocyte culture and which induces increased histamine synthesis by murine hematopoietic cells. It has been shown that it is different from interleukin 3 (IL 3), despite the fact that pure IL 3 expresses HCSF activity. Our results provide evidence that this factor (constitutively produced by the P388 D1 cell line) is identical with granulocyte-macrophage colony-stimulating factor (GM-CSF) i.e.: (a) physiochemical properties of HCSF and GM-CSF, such as molecular weight, isoelectric charge, hydrophobicity and behavior during affinity chromatography, are indistinguishable and both activities coelute during all biochemical purification procedures; (b) increased bone marrow cell histamine synthesis induced by P388 D1-derived HCSF is inhibited by anti-GM-CSF antiserum; (c) the GM-CSF cDNA probe hybridizes with a poly(A)+RNA from P388 D1 cells while no hybridizing signal was obtained with poly(A)+RNA from WEHI-3 and from P815 cells. On the other hand, the IL 3 cDNA probe hybridizes with a 1.0-kb poly(A)+RNA from WEHI-3 but not with those from P388 D1 and P815. Moreover, well known sources of GM-CSF, such as lung conditioned medium and semi-purified GM-CSF from phytohemagglutinin-induced supernatant of the murine T lymphoma LBRM-33-5 A4 (preparation devoid of IL 3), as well as recombinant murine GM-CSF, induce increased histamine synthesis by hematopoietic cells. All these results demonstrate that, in our culture conditions, the P388 D1 cell line spontaneously produces GM-CSF which is responsible for the P388 D1-induced HCS activity. Consequently, the latter is a property shared by the two distinct hematopoietic growth factors acting on the less committed cells, i.e. IL 3 and GM-CSF, whereas M-CSF or G-CSF are unable to induce histamine production. Interestingly, IL-4 which is known to support established mast cell line proliferation cannot induce HCS activity. In addition, none of the other cytokines tested, such as IL 1, IL 2, interferons or tumor necrosis factor can express HCS activity. This expression seems to be a specific property of IL 3 and GM-CSF.
Eur J Immunol 1987 Sep
PMID:Histamine-producing cell-stimulating activity. A biological activity shared by interleukin 3 and granulocyte-macrophage colony-stimulating factor. 288 59


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