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)

Monocyte chemotactic and activating factor (MCAF) is the most potent cytokine that activates basophils to release histamine. The response of human basophils to either simultaneous or sequential addition of the chemokines RANTES, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, platelet factor (PF)4, connective tissue activating peptide III (CTAP-III), interleukin (IL)-8, and inflammatory protein (IP)-10 on MCAF-induced histamine release was studied. Simultaneous addition of MCAF and any of the chemokines studied evoked an augmented response as measured by histamine release, whereas preincubation of leukocytes or purified basophils (80%) with these chemokines decreased MCAF-induced histamine release in a dose-dependent manner. Histamine release by anti-IgE remained unchanged. When tested at 5 x 10(-9) mol/L, the decrease in histamine release by RANTES was 69.2% +/- 3.5%, by MIP-1 alpha 48.8% +/- 3.1%, by MIP-1 beta 42.9% +/- 3.1%, by PF4 56.5% +/- 2.9%, by IL-8 41.2% +/- 2.2, by CTAP III 27% +/- 4.4%, and by IP-10 15.3% +/- 2.6%. The peak inhibition of histamine release by the chemokines was reached within 10 minutes of preincubation with basophils and remained unchanged thereafter. Washing basophils after preincubation with chemokines abolished the inhibition, with the exception of desensitization by low concentrations of MCAF. With the exclusion of MCAF and RANTES, none of the chemokines (at the concentration range of 5 x 10(-8) to 5 x 10(-11)) induced significant (> 10% above spontaneous) histamine release from basophils. Preincubation of basophils with C5a (5 x 10(-10) mol/L) did not affect histamine release, whereas preincubation with granulocyte-macrophage colony-stimulating factor (10 ng/ml) or IL-5 (10 ng/ml) enhanced MCAF-induced histamine release by 121.8% +/- 10.1% and 108% +/- 10.8%, respectively. We have therefore characterized RANTES, MIP-1 alpha, MIP-1 beta, CTAP III, PF4, IL-8, and IP-10 as inhibitors of MCAF-induced histamine release. Although the results are consistent with receptor blockade, the alpha and beta chemokines appear to interact with separate receptors linked to G proteins; thus, a mechanism of receptor class desensitization is proposed. Interaction of this group of cytokines at the site of allergic inflammation may modulate a function of basophils to initiate, augment, or inhibit histamine release.
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PMID:Chemokines of the alpha, beta-subclass inhibit human basophils' responsiveness to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1. 753 29

A number of cytokines have been implicated in the suppression of myeloid stem and progenitor cell proliferation. It has been suggested that some of these act directly on the stem/progenitors themselves, based on the effects of these cells, plated in culture at low seeding densities, on highly enriched populations. These studies, however, do not definitively rule out effects on accessory cells. To more rigorously evaluate direct-acting suppressive effects of cytokines, such cytokines were assessed for their effects on colony formation initiated by single bone marrow (BM) or umbilical cord blood (CB) CD34 cells sorted into single wells in the presence of a combination of growth-stimulating cytokines (erythropoietin [Epo], steel factor [SLF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and interleukin-3 [IL-3]) and in the presence or absence of serum. Under these conditions, it was demonstrated that H-ferritin, transforming growth factor-beta 1 (TGF-beta 1), and members of the chemokine family (macrophage inflammatory protein-1 alpha [MIP-1 alpha], MIP-2 beta, platelet factor 4 [PF4], IL-8, and macrophage chemotactic and activating factor [MCAF]) had direct significant suppressive activities on single stem/progenitor cells from adult human BM in the presence or absence of serum. Single sorted CB cells were much less sensitive to inhibition by these cytokines. The reasons for this differential sensitivity are not known. Of possible relevance to this for cytokines, such as H-ferritin and the chemokines that have actions during S-phase of the cell cycle, CB progenitors were in slower cycle at initiation of culture than were BM progenitors.
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PMID:Comparative effects of suppressive cytokines on isolated single CD34(3+) stem/progenitor cells from human bone marrow and umbilical cord blood plated with and without serum. 769 34

In a recent study, we showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) and supernatants from partially stimulated platelets undergoing selective alpha-granule release synergistically enhanced polymorphonuclear leukocyte (PMN) response to N-formyl-methionyl-leucyl-phenylalanine (fMLP). The active factor released from platelet alpha-granules was identified as platelet factor four (PF4). In this study we investigate the joint effect on PMN reactivity of GM-CSF and supernatants from platelets maximally stimulated to release both alpha- and dense granule contents. These platelet supernatants enhanced PMN chemiluminescence (CL; a measure of the oxidative burst) during short incubations, whereas longer incubations led to the loss of this enhancement and the prevention of PMN priming by GM-CSF. The platelet-derived inhibitory factor was of low molecular weight, originated from the dense granule precursor(s), and its generation required the presence of PMN. When ATP/ADP were incubated with PMN at concentrations found in platelet-dense granules, they produced a similar biphasic effect on PMN reactivity (a potentiation followed by inhibition) as seen with the platelet supernatants. The inhibitory effect of these nucleotides coincided with their conversion to AMP. AMP per se had an immediate inhibitory effect on PMN response to fMLP and prevented PMN priming by GM-CSF. This study confirms that partially stimulated platelets enhance PMN reactivity. However, during maximal stimulation, nucleotides released from the platelet-dense granules are converted to AMP, which in turn can counteract the PMN priming effects of factors such as PF4 and GM-CSF.
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PMID:Sequential potentiation and inhibition of PMN reactivity by maximally stimulated platelets. 906 Apr 55

The aim of this study was to explore how atrial natriuretic polypeptide (ANP) affects the properties and function of endothelial cells. Gene expression data GSE56976 generated at 0, 1, and 6 hours after ANP incubation in human umbilical vein endothelial cells (HUVEC) was used. Microarray data were preprocessed for differentially expressed genes (DEGs) in each time-dependent group. Next, gene ontology (GO), pathway analysis, and transcriptional regulation were performed. Co-expression clustering analysis of DEGs and functional enrichment analysis of co-expression modules were processed. RT-PCR analysis was performed to validate gene expression. DEGs were obtained and their counts were increased from 0 hours to 6 hours. No overlapping DEGs were obtained among the 3 groups. The DEGs of ANP_6hours, including TGFB2 (transforming growth factor, beta 2), LTF (lactotransferrin/lactoferrin), and ETV7 (Ets variant 7) were mainly related with cell apoptosis and immune responses. The DEGs in the network of ANP_0hour were mainly associated with epithelial ion transport processes. In addition, 3 co-expressed modules were detected. CSF2 (colony stimulating factor 2) and PF4 (platelet factor 4) of the blue module were related with cytolysis, while FXYD1 (FXYD domain containing ion transport regulator 1) and TGFB2 of the yellow module were mainly enriched in ion transport and the ovulation cycle. The expression of TGFB2 obtained by microarray analysis was consistent with that of RT-PCR. Ion transport could be affected promptly after ANP treatment, and subsequently, the cytolysis of vein endothelial cells may be promoted and endothelial permeability would be enhanced, followed by activated immune responses.
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PMID:Transcriptional Analysis of Endothelial Cell Alternation Induced by Atrial Natriuretic Polypeptide in Human Umbilical Vein Endothelial Cells. 2927 24