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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)

Priming of neutrophil oxidative responses by granulocyte-macrophage colony-stimulating factor (GM-CSF) has been well documented, but its inhibitory effect on chemotaxis has led to concerns that its therapeutic administration may compromise neutrophil emigration to sites of infection and inflammation. We developed a murine model to determine the biodistribution kinetics of [111In] labeled neutrophils and used this model to study the influence of recombinant GM-CSF on neutrophil influx into inflammatory sites. Murine neutrophils were harvested from the peritoneal exudate 3 h after the intraperitoneal injection of fluid thioglycollate medium, radiolabeled with [111In]tropolonate, and resuspended in 10% acid/citrate/dextrose: 90% Hanks' balanced salt solution (without Ca2+ and Mg2+) at pH 6.5 for re-injection. To assess the in vivo effect of GM-CSF, 22 mice were injected intravenously with labeled neutrophils 1 h prior to intraperitoneal challenge with thioglycollate or saline. Half of the mice also received 2.0 micrograms of recombinant murine GM-CSF intravenously at the time of injection of labeled cells. GM-CSF had no influence on the influx of labeled cells to the peritoneum of animals that received i.p. saline, but increased by nearly 50% the cellular migration elicited by i.p. injection of thioglycollate. We conclude that GM-CSF does not impair, but rather enhances, the ability of circulating neutrophils to respond to thioglycollate-induced inflammation in vivo. The model we describe provides a useful and controllable method to investigate the effects of GM-CSF and other cytokines on the biodistribution kinetics and emigration of neutrophils in vivo.
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PMID:Granulocyte-macrophage colony-stimulating factor enhances exudation of neutrophils to sites of inflammatory challenge in vivo. 213 78

The possible direct antigen formation of Ni2+ on antigen-presenting cells (APCs) was studied with cultured human dendritic cells (DCs) obtained from 10 subjects contact allergic to Ni2+ and six non-allergic control individuals. All contact allergic subjects showed a significantly increased peripheral blood mononuclear cell (PBMC) response in vitro to Ni2+. DCs were expanded from the plastic-adherent cell fraction of PBMCs by culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 7 days to obtain immature DCs, and with the addition of monocyte-conditioned medium for another 4 days, for DC maturation. The DCs were pulsed for 20 min with Ni2+ (50 micrometers) in protein-free Hank's balanced salt solution (HBSS) and added to freshly prepared autologous responder PBMCs. With five allergic subjects, immature DCs pulsed with Ni2+ demonstrated a significant capacity to activate Ni2+-reactive lymphocytes. With the remaining five patients and the six controls no difference in lymphocyte proliferation was observed between Ni2+-pulsed and non-pulsed immature DCs. In contrast, with mature Ni2+-pulsed DCs from both 'positive responder' (n=4) and 'non-responder' (n=4) patients, there was a significantly stimulated PBMC proliferation, whereas with the controls (n=4) still no activation was observed. Our results indicate that direct formation of the antigenic determinant of Ni2+ on APCs is possible and that Ni2+ uptake and processing mechanisms may not play a major role. Differences in the ease of activation of Ni2+-reactive lymphocytes are discussed in terms of a possible heterogeneity in the availability of Ni2+-reactive groups presented on endogenous peptides bound in the antigen binding groove of human leucocyte antigen (HLA) class-II molecules.
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PMID:Direct Ni2+ antigen formation on cultured human dendritic cells. 1023 44