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)

We assessed the expression of the adhesion molecules leukocyte function antigen-1 (LFA-1, CD11a), intercellular adhesion molecule-1 (ICAM-1, CD54), homing-associated cell adhesion molecule (H-CAM, CD44), and c-kit (stem cell factor receptor) on the CD34+ progenitor population from the leukapheresis products of 23 patients (LP CD34+). For blood stem cell collection granulocyte colony-stimulating factor (G-CSF) or interleukin-3/granulocyte-macrophage colony-stimulating factor (IL-3/GM-CSF) was administered after cytotoxic chemotherapy. Furthermore, bone marrow- and blood-derived CD34+ progenitor cells from 6 normal volunteers (BM and PB CD34+) were analyzed. LFA-1 expression was higher on PB CD34+ (88.2 +/- 2.5%, mean +/- SEM) than on BM CD34+ (75.3 +/- 4.3%). Following cytokine administration, LFA-1 was expressed on only 59.7 +/- 3.7% of LP CD34+ at a low fluorescence intensity, suggesting that down-regulation of LFA-1 may facilitate the egress of cells from the bone marrow and prolong their circulation. In contrast, ICAM-1 was weakly positive on CD34+ cells from all sources. CD44 was expressed on the vast majority of CD34+ cells (> 95%) in all samples studied. The highest proportion of CD34+ cells costaining for c-kit was found in normal bone marrow (32.2 +/- 3.3%). In normal peripheral blood and after cytokine mobilization, fewer of the CD34+ cells weakly expressed c-kit (< 15%). The low percentage and level of c-kit expression may indicate that the majority of cytokine-mobilized CD34+ cells are lineage-committed progenitor cells, as reflected by the coexpression pattern for CD38, HLA-DR, and CD33.
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PMID:Expression of adhesion molecules and c-kit on CD34+ hematopoietic progenitor cells: comparison of cytokine-mobilized blood stem cells with normal bone marrow and peripheral blood. 752 8

In the absence of conclusive assays capable of determining the functionality of ex vivo expanded human hematopoietic progenitor cells, we combined cell tracking with the membrane dye PKH2, immunostaining for CD34, and limiting dilution analysis to estimate the frequency of long-term hematopoietic culture-initiating cells (LTHC-ICs) among de novo-generated CD34+ cells. Umbilical cord blood (CB) and bone marrow (BM) CD34+ cells were stained with PKH2 on day 0 and cultured with stem cell factor (SCF) and interleukin-3 (IL-3) in short-term stromal cell-free suspension cultures. Proliferation of CD34+ cells in culture was tracked through their PKH2 fluorescence relative to day 0 and the continued expression of CD34. As such, it was possible to identify cells that had divided while maintaining the expression of CD34 (CD34+PKH2dim) and others that expressed CD34 but had not divided (CD34+PKH2bright). In all such cultures, a fraction of both BM and CB CD34+ cells failed to divide in response to cytokines and persisted in culture for up to 10 days as CD34+PKH2bright cells. Between days 5 and 7 of culture, CD34+PKH2bright and CD34+PKH2dim cells were sorted in a limiting dilution scheme into 96-well plates prepared with medium, SCF, IL-3, IL-6, granulocyte-macrophage colony-stimulating factor, and erythropoietin. Cells proliferating in individual wells were assayed 2 weeks later for their content of clonogenic progenitors and the percentage of negative wells was used to calculate the frequency of LTHC-ICs in each population. Among fresh isolated BM and CB CD34+ cells, the frequencies of LTHC-ICs were 2.01% +/- 0.98% (mean +/- SEM) and 7.56% +/- 2.48%, respectively. After 5 to 7 days in culture, 3.00% +/- 0.56% of ex vivo-expanded BM CD34+PKH2bright cells and 4.46% +/- 1.10% of CD34+PKH2dim cells were LTHC-ICs. In contrast, the frequency of LTHC-IC in ex vivo expanded CB CD34+ cells declined drastically, such that only 3.87% +/- 2.06% of PKH2bright and 2.29% +/- 1.75% of PKH2dim cells were determined to be initiating cells after 5 to 7 days in culture. However, when combined with a calculation of the net change in the number of CD34+ cells in culture, the sum total of LTHC-ICs in both BM and CB cells declined in comparison to fresh isolated cells, albeit to a different degree between the two tissues.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evaluation of ex vivo expansion potential of cord blood and bone marrow hematopoietic progenitor cells using cell tracking and limiting dilution analysis. 753 90

The effects of interleukin (IL)-2, -3, -4, -5, -6, and -7 and granulocyte-macrophage colony-stimulating factor (GM-CSF) on histamine release from human basophils were evaluated. IL-3 was the only cytokine with histamine-releasing activity. This activity was observed predominantly on basophils from allergic patients (mean release +/- SEM, 33.9 +/- 9.5%; n = 12), whereas basophils from normal subjects responded less frequently to stimulation with IL-3 (mean release +/- SEM, 2.8 +/- 1.0%; n = 22). The effect of IL-3 was time and temperature dependent, since release was optimal after incubation for 120 min at 37 degrees C. When cell-bound IgE were eluted at acid pH, basophils became unresponsive to IL-3; however, IL-3-induced histamine release correlated with anti-IgE-induced histamine release in allergics, but not in normals. IL-3, IL-5, IL-6, and GM-CSF enhanced significantly anti-IgE- and FMLP-induced histamine release. In contrast, IL-2, IL-4, and IL-7 were devoid of any significant histamine-releasing or -potentiating activity. These results indicate that IL-3 can induce and IL-3, -5, and -6 and GM-CSF can enhance histamine release from human basophils, suggesting a possible role of these cytokines in the expression of allergic reactions.
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PMID:Inducing and enhancing effects of IL-3, -5, and -6 and GM-CSF on histamine release from human basophils. 768 60

The aims of this study were: to quantify immunoreactive tumour necrosis factor alpha (TNF-alpha) concentrations in maternal plasma and amniotic fluid obtained from women during pregnancy and labour, both at term and preterm; and to establish the effects of bacterial endotoxin and cytokines on the in vitro release of TNF-alpha from intrauterine tissues. Maternal plasma TNF-alpha concentrations did not change during pregnancy (457.2 +/- 102.9 ng/l, mean +/- SEM, N = 52) or at the time of labour (543.5 +/- 138.6 ng/l, N = 43). In contrast, amniotic fluid TNF-alpha concentrations increased significantly (p < 0.05) during pregnancy (early pregnancy, EP, 93.0 +/- 24.8 ng/l, N = 7; preterm not-in-labour, PNIL, 186.8 +/- 42.9 ng/l, N = 16; term not-in-labour. TNIL, 499.7 +/- 150.9 ng/l, N = 13) and in association with preterm labour (preterm in-labour, PIL, 958.7 +/- 575.6 ng/l, N = 5 vs PNIL, 186.8 +/- 42.9 ng/l, N = 16). Choriodecidual and placental explants (N = 3) maintained in in vitro culture released TNF-alpha. Furthermore, the release of TNF-alpha was increased significantly (p < 0.05) by bacterial endotoxin (lipopolysaccharide, 10 ng/l-10 mg/l) but was not affected by the following cytokines at the indicated doses: interleukin-1 alpha (0.28 nmol/l), interleukin-6 (12.5 nmol/l), granulocyte colony-stimulating factor (2.5 nmol/l), granulocyte-macrophage colony-stimulating factor (35 nmol/l), macrophage colony-stimulating factor (1.2 nmol/l), leukaemia inhibitory factor (0.45 nmol/l) and transforming growth factor-beta (0.4 nmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumour necrosis factor alpha during human pregnancy and labour: maternal plasma and amniotic fluid concentrations and release from intrauterine tissues. 780 44

To study human eosinophils, their efficient purification from peripheral blood is crucial. Although a number of purification procedures, including discontinuous Percoll and metrizamide density gradient centrifugation, have been used, it has been difficult to isolate eosinophils from normal donors with consistently high yields and purities. Recently, a new isolation technique called magnetic cell separation system (MACS) was reported. To evaluate this procedure, we isolated eosinophils from human peripheral blood using either MACS or the standard discontinuous Percoll density methods, and compared cellular viability, morphology, and response to degranulation stimuli. MACS gave a higher yield of eosinophils than Percoll density centrifugation; for example, 6.6 +/- 1.1 x 10(6) eosinophils were isolated from 20 ml of blood by MACS compared to 6.4 +/- 2.4 x 10(6) from 120 ml by Percoll density gradient. Further, the purity of eosinophils isolated by MACS was 97.1 +/- 0.5% (X +/- SEM) compared to 77.8 +/- 2.9% with Percoll. As part of the MACS protocol, erythrocytes are lysed with either 155 mM ammonium chloride or hypotonic lysis. With 155 mM ammonium chloride treatment, the eosinophils showed a striking reduction in cytokine mediated survival due to interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF), marked morphologic abnormalities and a reduced degranulation response. With hypotonic lysis, no differences were observed in survival and morphology between eosinophils purified by MACS and Percoll methods; the degranulation responses to stimuli were essentially the same between the two methods. Taken together, these observations suggest that the exposure of eosinophils to 155 mM ammonium chloride results in cellular damage. Therefore, MACS with hypotonic lysis is a useful technique to isolate eosinophils for biological study.
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PMID:Ammonium chloride exposure inhibits cytokine-mediated eosinophil survival. 830 93

Tumor infiltrating lymphocytes (TIL) were cultured from 17 B-cell lymphoma specimens derived from patients with predominantly low-grade malignancies. Specimens included 15 lymph-node biopsies, 1 malignant pleural effusion, and PBL from 1 patient with circulating lymphoma cells. The phenotypic and proliferative characteristics of TIL cultured in interleukin-2 (IL-2) were studied, as well as cytolysis and cytokine secretion in response to autologous tumor. Flow cytometry of fresh tumor suspensions showed that 50% of cells (median) were malignant B cells and 36% were infiltrating T lymphocytes. After culture for approximately 1 month, TIL were 75% +/- 8% CD3+ (mean +/- SEM), 47% +/- 8% CD4+ and 35% +/- 7% CD8+. TIL proliferation was modest in most cases: the median maximum expansion was 32-fold in 25 days. Lysis of autologous tumor in 4-hour 51Cr release assays was mediated by 2 of 12 TIL studied, but was nonspecific. However, these same two TIL, when cocultured with various tumor stimulators, preferentially secreted tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor after autologous tumor stimulation; unstimulated TIL secreted undetectable or barely detectable levels of these cytokines. In one TIL culture, cytokines were secreted by purified CD4+ TIL but not by CD8+ cells, and secretion was completely abrogated by the anti-major histocompatibility complex (MHC) class II antibody IVA12. Thus, although specific cytokine secretion by lymphoma TIL in response to autologous tumor was observed, it occurred in fewer than 20% of patients studied.
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PMID:Tumor-infiltrating lymphocytes derived from select B-cell lymphomas secrete granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha in response to autologous tumor stimulation. 835 84

The regulatory role of leukotrienes (LT) on human myelopoiesis was investigated. Mononuclear bone marrow cells from 31 healthy donors were cultivated in the presence of suboptimal concentrations of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) for 10 days in semisolid agar. The addition of LTC4 or LTB4 to the cultures dose-dependently stimulated myeloid stem cell proliferation. Maximal effects were observed at 10(-8) mol/L, at which LTC4 induced a 91% +/- 23% (mean +/- SEM; P = .004) and LTB4 a 73% +/- 22% (P = .008) increase in colony formation. In contrast, addition of the LTB4 isomer 5(S), 12(S)-diHETE did not affect the growth. LTD4 exerted a weak potentiating effect on progenitor proliferation (17% +/- 7% growth stimulation at 10(-10) mol/L; P = .034), whereas LTE4 was without consistent effect. Furthermore, LTC4-induced stimulation of colony formation was insensitive to the LTD4 antagonist ICI 198615. The dual lipoxygenase and prostaglandin endoperoxide synthase inhibitor CL42A potently suppressed the proliferation of myeloid colonies, a suppression that could be reversed by parallel addition of LTB4 or LTC4. The results suggest that both LTB4 and LTC4 possess strong and specific synergistic stimulatory effects on GM-CSF-induced human myeloid progenitor cell growth.
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PMID:Stimulation of human myelopoiesis by leukotrienes B4 and C4: interactions with granulocyte-macrophage colony-stimulating factor. 838 Jul 23

We have previously shown that surface levels of the adhesive glycoprotein, L-selectin, are diminished on cord blood neutrophils (polymorphonuclear leukocytes, PMN) and associated with impaired adherence to endothelium under flow conditions. To test the hypothesis that diminished surface levels reflect a total cellular deficiency, we measured L-selectin in PMN lysates and plasma from cord and adult blood. L-selectin content was decreased in cord blood PMN lysates compared with those of adults by both Western blot analyses and ELISA (cord blood, 1195 +/- 160 pg/mL; adult, 1870 +/- 260 pg/mL; X +/- SEM; p < 0.05). Soluble L-selectin levels were also decreased in cord blood plasma (324 +/- 24 ng/mL versus 537 +/- 28 ng/mLiter in adult plasma, p < 0.01). To evaluate L-selectin function, we next compared the dose dependent effect of several chemoattractants on shedding of L-selectin from cord blood and adult PMN. Adult PMN showed greater overall shedding of L-selectin as compared with cord blood PMN after stimulation with fMet-Leu-Phe (p < 0.03) and granulocyte-macrophage colony-stimulating factor (p < 0.02). In contrast, shedding of L-selectin was similar between groups after IL-8 tested stimulation. We conclude that cord blood PMN have a decreased cellular content of L-selectin in addition to an impaired ability to shed surface L-selectin in response to specific inflammatory mediators.
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PMID:Diminished soluble and total cellular L-selectin in cord blood is associated with its impaired shedding from activated neutrophils. 884 34

The aim of this study was to assess prospectively the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of chemotherapy-induced oral mucositis in non-neutropenic cancer patients. In a prospective open study, 30 cancer patients with chemotherapy-induced, neutropenia-independent oral mucositis were treated with GM-CSF (Schering Plough Corp, Kenilworth, NJ) prepared as a mouthwash solution (5-10 micrograms ml-1). GM-CSF was administered within 24 hours of occurrence of oral mucositis x 4 to 6 times daily. Systemic GM-CSF was not permissible. Oral mucositis was graded according to the modified Radiation Therapy Oncology Group criteria. Six patients were subsequently excluded as they experienced neutropenia during GM-CSF therapy. The remaining 24 patients were all evaluable. Most patients had either Grade 3 or 4 gross (76%) or functional (54%) mucositis. The mean +/- SEM gross oral mucositis scores for all 24 patients combined decreased from 3.08 +/- 0.18 at baseline to 2.04 +/- 0.19 (p < 0.0001) after 2 days, 0.92 +/- 0.16 (p < 0.0001) after 5 days, and 0.25 +/- 0.09 (p < 0.0001) after 10 days of therapy. Likewise, the mean +/- SEM functional oral mucositis scores decreased from 2.71 +/- 0.18 at baseline to 1.58 +/- 0.19 (p < 0.0001) after 2 days, 0.75 +/- 0.16 (p < 0.0001) after 5 days, and 0.17 +/- 0.08 (p < 0.0001) after 10 days of therapy. The duration of severe oral mucositis was also shortened as Grade 0 or 1 (gross mucositis score) was evident in seven (29%), 20 (83%), and 24 (100%) patients by the 2nd, 5th, and 10th day of therapy, respectively. Similarly, Grade 0 or 1 (functional mucositis score) reported in 13 (54%), 19 (79%), and 24 (100%) by the 2nd, 5th, and 10th day of therapy respectively. It was found that GM-CSF mouthwash as used in this study has a significant recuperative efficacy on the severity, morbidity, and duration of chemotherapy-induced oral mucositis. A large randomized, placebo-controlled study is warranted to ascertain that benefit and determine the optimal dosages and schedule.
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PMID:Effect of granulocyte-macrophage colony-stimulating factor on chemotherapy-induced oral mucositis in non-neutropenic cancer patients. 923 12

To investigate the immunomodulatory impact of low-dose recombinant human interleukin-6 (rhIL-6), we examined 15 patients with metastatic renal cell carcinoma or malignant melanoma receiving rhIL-6 as an antitumor agent in a phase II trial. RhIL-6 (150 micrograms) was administered subcutaneously (s.c.) once daily for 42 consecutive days. Immunologic parameters were measured throughout therapy and at follow-up. No changes in white blood cell counts were noted. Lymphocyte subsets did not alter, nor did their expression of CD25 and HLA-DR. Immunoglobulins were unaffected. Levels of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha and IL-1 beta remained below detection limits. Theoretically, subtle immunologic alterations might have been masked by increases in plasma volume, known to occur after start of therapy. Using previously published data concerning plasma volume changes in these patients, part of immunologic data were corrected for concurrent hemodilution, showing a 39% +/- 17% increase in monocytes (mean change +/- SEM [standard error of mean]; p < 0.03) within 1 week of therapy, while lymphocytes tended to increase. However, the absence of appreciable increases in cell activation markers and in monokine levels indicates insufficient immune activation, probably underlying the lack of objective antitumor responses (6 x stable, 9 x progressive disease) in these patients. In conclusion, the immunomodulatory impact of rhIL-6, if present at all, remains very limited.
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PMID:The modulatory impact of recombinant human interleukin-6 on the immune system of cancer patients. 1040 38


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