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 intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor to three patients with leukemia who were receiving marrow aplasia-inducing chemotherapy resulted in the development of wide-spread erythematous macules and papules. The course of the eruption paralleled the time of infusion of the granulocyte-macrophage colony-stimulating factor. Skin biopsy specimens taken from two of the eruptions displayed characteristic changes consisting of a variable mixture of granulocytes and lymphocytes, increased number and size of dermal macrophages, mild to moderate epidermal exocytosis, intercellular edema, and rare dyskeratotic keratinocytes. Immunophenotypic analysis of one specimen was notable for keratinocyte intercellular adhesion molecule-1 expression. Administration of the recombinant human cytokine in pharmacologic doses is postulated to induce changes in the immunologic status of the skin, resulting in the expression of a cutaneous eruption.
Arch Dermatol 1991 Jan
PMID:Intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor causes a cutaneous eruption. 182 45

Cutaneous eruptions displaying perivascular inflammatory cell infiltrates histologically may develop with the intravenous administration of cytokines. Similar findings are seen spontaneously in some patients on recovery of peripheral blood lymphocytes after profound marrow aplasia. To investigate the production of a cutaneous perivascular infiltrate further, the ability of several cytokines to induce a perivascular lymphocytic infiltrate was studied in vitro using a skin explant model. A skin biopsy specimen obtained at the time of peripheral blood lymphocyte recovery after chemotherapy-induced marrow aplasia (n = 10) was divided and incubated for 3 days with and without a series of cytokines plus various peripheral blood mononuclear cell populations. Skin incubated with interleukin 2 and granulocyte-macrophage colony-stimulating factor induced a perivascular lymphocytic infiltrate, while control samples did not. Immunophenotypic analysis revealed that the lymphocytes were predominantly CD3+/CD4+. An infiltrate was not observed when skin was incubated with cytokines alone, without the addition of simultaneously isolated peripheral lymphocytes. A perivascular pattern was not observed with the addition of interferon gamma. Only interferon gamma induced keratinocyte intercellular adhesion molecule 1 expression in experimental tissue. Certain cytokines that affect a range of cell types are capable of inducing a common cutaneous histologic pattern, the perivascular lymphocytic infiltrate.
Arch Dermatol 1991 Dec
PMID:Interleukin 2 and granulocyte-macrophage colony-stimulating factor induce a perivascular lymphocytic infiltrate in a skin explant model. 184 77

Keratinocytes are a potent source of a variety of cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF). In this study, we have shown that ultraviolet B (UVB) irradiation augments GM-CSF mRNA expression by murine keratinocytes. This is reflected in the increased production of GM-CSF protein by these cells. In the same cell population, exposure to UVB irradiation increases interleukin 1 alpha (IL-1 alpha) mRNA and IL-1 protein as detected by bioactivity. This increase in IL-1 alpha precedes the increase of GM-CSF mRNA. Addition of recombinant IL-1 alpha to the medium increases GM-CSF mRNA expression. Anti-IL-1 alpha antibodies can completely inhibit UV-augmented GM-CSF mRNA expression. These results demonstrate that UVB irradiation-induced augmentation of GM-CSF is mediated by UV-induced IL-1 alpha.
J Invest Dermatol 1991 Jul
PMID:Augmentation of granulocyte/macrophage colony-stimulating factor expression by ultraviolet irradiation is mediated by interleukin 1 in Pam 212 keratinocytes. 205 79

We investigated the ability of the purified recombinant human cytokines: tumor necrosis factor-alpha (rTNF), granulocyte-macrophage colony-stimulating factor (rGM-CSF), interleukin-1 beta (rIL-1), interleukin-3, and tumor necrosis factor-beta (rTNF-beta) to stimulate neutrophil adherence (NA) to basement membranes (BMs) of stratified squamous epithelia pretreated with autoantibodies (ABM) specific for the BM matrix protein, type-VII collagen. rTNF, rGM-CSF, rIL-1, and rTNF-beta, but not IL-3, stimulated NA and stimulation was ABM- and cytokine-concentration-dependent. Stimulation was cytokine-specific and not due to endotoxin since it was significantly inhibited by cytokine-specific antibodies but not by polymyxin B (PB). rTNF and rGM-CSF were the most potent stimulators, were effective at concentrations less than 0.067 ng/ml, and stimulated NA greater than 600%. Relative potency was: rTNF = rGM-CSF greater than rTNF-beta greater than rIL-1. Stimulation by rTNF was due to a rapid, time-dependent effect on the neutrophil, and NA appeared to be dependent, in part, on the low-affinity neutrophil receptor for IgG, Fc(gamma)RIII, because it could be specifically inhibited by monoclonal antibody (3G8) to Fc(gamma)RIII. These results suggest that rTNF, rGM-CSF, rIL-1, and rTNF-beta may contribute individually or in combination to immune-mediated inflammation and tissue injury by stimulating immune adherence of neutrophils to tissue-bound autoantibodies and immune complexes.
J Invest Dermatol 1990 Aug
PMID:Recombinant human cytokines stimulate neutrophil adherence to IgG autoantibody-treated epithelial basement membranes. 219 82

Activated polymorphonuclear neutrophilic granulocytes (PMN) play an important role in propagation of inflammatory reactions and are capable of mediating tissue damage particularly by release of reactive oxygen species and lysosomal contents. Cytokines produced by monocytes as well as epidermal cells were recently shown to modulate PMN function. Therefore, the effect of immunomodulating cytokines on the oxidative metabolism of isolated human PMN was tested by functional as well as ultrastructural criteria. The following recombinant human cytokines were tested: tumor necrosis factor (TNF alpha), lymphotoxin (TNF beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, G-CSF, PDGF, TGF-beta, interleukin-1 (IL-1) alpha and beta, IL-2, IL-3, IL-4, IL-5, IL-6, MONAP/MOC/NAF (IL-8), interferon-alpha and -gamma. Only TNF alpha, TNF beta and GM-CSF were found to be direct stimuli of the oxidative burst in human PMN whereas IL-3, IL-5, and IL-8 were active only at extremely high concentrations. None of the other cytokines tested induced any significant effect on isolated human PMN at physiological concentrations. The results clearly demonstrate that only selected cytokines are capable of inducing a long lasting activation of PMN oxidative metabolism. Release of these mediators represents a specific signal for PMN activation in inflammatory disease states.
J Invest Dermatol 1990 Dec
PMID:Activation of the oxidative metabolism in human polymorphonuclear neutrophilic granulocytes: the role of immuno-modulating cytokines. 225 41

In order to clarify the role played by immunologically derived cytokines in dermal connective tissue synthesis and degradation, we investigated the effect of human recombinant (hu-r) interleukin (IL) 1-alpha and beta, hu-r tumor necrosis factor (TNF)-alpha and beta, hu-r IL 2, and hu-r granulocyte-macrophage colony-stimulating factor (GM-CSF) on the production of collagen, glycosaminoglycan, fibronectin, and collagenase activity by three lines of cultured human adult dermal fibroblasts. Our results show that 24-72 h treatment of confluent fibroblast cultures with IL 1-alpha or beta or TNF-alpha or beta causes concentration (1 to 1 X 10(4) U/ml) dependent increases in collagen, glycosaminoglycan, and collagenase activity production, but decreases in fibronectin production. In contrast, treatment with IL 2 and GM-CSF had no effect on fibroblast functions. The data show that IL 1-alpha and beta and TNF-alpha and beta differentially regulate fibroblast functions, and that increases in catabolic functions like collagenase activity production are more than tenfold greater than increases in anabolic functions like collagen production. When these results are considered along with other reports, they suggest that IL 1 and TNF may play predominately a catabolic role in situ during dermal fibrotic responses by directly inhibiting fibronectin production and indirectly causing the degradation of collagen and glycosaminoglycan by significantly increasing dermal fibroblast elaboration of collagenase and proteoglycanase activities.
J Invest Dermatol 1989 May
PMID:Differential regulation of collagen, glycosaminoglycan, fibronectin, and collagenase activity production in cultured human adult dermal fibroblasts by interleukin 1-alpha and beta and tumor necrosis factor-alpha and beta. 254 Dec 8

We have examined the effects of four well-characterized cytokines with T lymphocyte-stimulatory activity, i.e., interleukin (IL)-2, IL-3, IL-4, and granulocyte-macrophage colony-stimulating factor (GM-CSF) on [3H]-thymidine incorporation in peripheral blood mononuclear cells (PBMs) obtained from patients with psoriasis. Under the influence of these cytokines, the incorporation of [3H]-thymidine into the PBMs was not different between psoriatic patients and healthy controls either in culture supplemented with pooled AB serum or with autologous serum. However, a potent immunopotentiator OK-432, which is a lyophilized preparation of penicillin-treated low virulence Su-strain of Streptococcus pyogenes group A3, induced significantly less incorporation of [3H]-thymidine into the PBMs from psoriatic patients than those from healthy controls [in both the culture supplemented with pooled AB serum (p less than 0.01) and that with autologous serum (p less than 0.01)]. This reduction in thymidine uptake was closely related to the disease activity as well as to the extent of skin lesions of the psoriatic patients. The defective immune response of PBMs from psoriatic patients to OK-432 probably reflects an abnormality at the level of interaction between monocytes and T cells or at the subsequent production and release of cytokines by them.
Arch Dermatol Res 1989
PMID:Proliferative responses of peripheral blood mononuclear cells from psoriatic patients to T lymphocyte-stimulating cytokines (IL-2, IL-3, IL-4, and granulocyte-macrophage colony-stimulating factor) and OK-432. 267 7

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was shown to modulate different granulocyte functions. In the present study we investigated the effect of purified and recombinant human GM-CSF, particularly on the oxidative metabolism of isolated human granulocytes. In addition, ultrastructural changes upon stimulation were evaluated. For detection of granulocyte activation the following assay systems were used: 1) lucigenin-dependent chemiluminescence (CL), 2) superoxide-dismutase (SOD) inhibitable cytochrome C-reduction (superoxide), 3) horseradish peroxidase-mediated oxidation of phenol red (hydrogen peroxide), 4) release of myeloperoxidase, 5) ultrastructural detection of hydrogen peroxide-production, and 6) scanning and transmission electron microscopy (SEM and TEM, respectively). A significant CL response was seen upon stimulation with recombinant human GM-CSF at concentrations ranging from 1 to 10(3) U/ml. The CL response started within 5-10 min with a maximum at 60-90 min and lasted more than 3 h. Thereafter granulocytes were completely deactivated to restimulation with the same mediator and with Tumor Necrosis Factor, but responded to other triggers of the oxidative burst, whereas the response to f-met-leu-phe was significantly increased. The CL signal was completely blocked by an antiserum to GM-CSF. Moreover, the response was significantly inhibited by SOD and D-Mannitol, suggesting the involvement of distinct reactive oxygen species (ROS) in generating the CL response. Significant amounts of superoxide were detected within 180 min after stimulation with GM-CSF, whereas release of hydrogen peroxide and peroxidase were only minimal as shown by functional and ultrastructural assays. Activation of granulocytes could be visualized by SEM and TEM. GM-CSF stimulated cells showed an increased adherence to the substratum developing polarized filopodia and an increased number of intracellular vesicles within 30 min after addition of the stimulus. The results clearly demonstrate that GM-CSF directly stimulates granulocytes and, particularly, their oxidative metabolism. Therefore, GM-CSF which is probably released by epidermal cells appears to be a candidate for neutrophil activation in the skin, and thereby may play a crucial role in inflammatory skin diseases.
J Invest Dermatol 1988 Jul
PMID:Human granulocyte-macrophage colony stimulating factor: an effective direct activator of human polymorphonuclear neutrophilic granulocytes. 283 54

The V gamma 5/V delta 1(+)-T-cell receptor (TCR)-bearing T-cell clone, 2CBET-3, was generated from C57BL/6 mice. Upon stimulation, 2CBET-3 cells produce interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha, but not IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, macrophage colony-stimulating factor, or interferon-gamma. These cells were evaluated for their ability to be stimulated by a variety of murine cell lines, including fibroblasts, trophoblasts, melanoma cells, embryonic carcinomas, B-cell lymphomas, mastocytoma cells, and keratinocytes. The human B-lymphoma cell line, Daudi, also was included in these studies. We found that 2CBET-3 cells produced cytokines up to several hundredfold above the control levels in response to the B-cell lines, Daudi, and A20/2J, but not to the B-cell line 439.4.2. After fixation with glutaraldehyde, Daudi and A20/2J continued to stimulate this gamma delta T-cell line. 2CBET-3 cells also responded to the keratinocyte line PAM212, but not to another, XB-2. When lipopolysaccharides (LPS) from Escherichia coli or S. typhimurium were added to 2CBET-3 cells in the presence of A20/2J cells, 2CBET-3 cells responded with increased cytokine production compared with the cytokine production in the presence of A20/2J cells alone. 2CBET-3 cells by themselves did not respond to LPS alone or to supernatants from A20/2J cells incubated with LPS. Unlike 2CBET-3, the epidermal T-cell hybridoma 70BET-49, expressing a V gamma 5/V delta 1-TCR identical to that of 2CBET-3, did not respond to A20/2J cells in the presence or absence of LPS, suggesting a requirement for molecules other than the TCR for V gamma 5/V delta 1-TCR+ T-cell stimulation by the B-cell lines and by LPS. This unique reactivity of gamma delta-TCR+ cells is different from that of alpha beta-TCR+ cells and may reflect a functional specialization of gamma delta-TCR+ cells in the response to bacterial infections.
J Invest Dermatol 1995 Jul
PMID:Murine epidermal V gamma 5/V delta 1-T-cell receptor+ T cells respond to B-cell lines and lipopolysaccharides. 761 98

Disseminated fungal infections commonly occur in immunocompromised hosts; Candida spp. are the most common. Fusarium spp., soil saprophytes once considered pathogenic only in plants, have emerged as serious pathogens in neutropenic patients with malignancies. We describe two patients, one with acute myelogenous leukemia and the other with metastatic breast cancer, in whom disseminated Fusarium solani infection developed. Both patients had neutropenia and fever when generalized, tender, erythematous papules developed; most of the papules had black necrotic centers. Despite aggressive therapy with antifungal agents and granulocyte-macrophage colony-stimulating factor, both patients died within 1 month. Disseminated Fusarium infection can be a life-threatening condition in which skin lesions are frequently the initial sign. Early recognition and hematopoietic recovery offer the best chance for survival.
J Am Acad Dermatol 1995 Feb
PMID:Disseminated Fusarium solani infection. 782 38


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