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 LFA-1 adhesion molecule is involved in cell adhesion events of leukocytes through binding to ICAM-1, ICAM-2 and ICAM-3. Whether binding to either of these ligands similarly affects co-stimulation of T cells and cytokine secretion is unknown. We demonstrated that LFA-1 co-stimulation under suboptimal concentrations of anti-CD3 monoclonal antibodies resulted in high, intermediate and weak proliferation of T cells on ICAM-1, -2, and -3, respectively, which correlates with the distinct affinities of LFA-1 for these ligands. Furthermore, we investigated whether binding to ICAM-1, -2 or -3 induced different cytokine profiles, thus regulating T helper cell function. Granulocyte-macrophage colony-stimulating factor and IFN-gamma were secreted in high amounts, whereas IL-2, IL-4 and IL-5 could not be detected. Interestingly, we observed that LFA-1/ICAM-1 co-stimulation of T cells resulted in high production of the Th2 cytokine IL-10 compared to ICAM-2 or ICAM-3 co-stimulation. In contrast, ICAM-2 and ICAM-3 induced a much stronger secretion of the Th1 cytokine TNF-alpha compared to LFA-1/ICAM-1 induced co-stimulation, despite the lower proliferation rate. These results demonstrate that besides facilitating cell adhesion, LFA-1 serves as a potent co-stimulatory molecule by inducing different cytokine patterns depending on the ligand bound.
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PMID:Co-stimulation of T cells results in distinct IL-10 and TNF-alpha cytokine profiles dependent on binding to ICAM-1, ICAM-2 or ICAM-3. 1042 88

Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances and primes monocyte functions, but its role in monocyte migration is poorly understood. We examined monocyte migration across human umbilical vein endothelial cells (HUVEC) grown on filters. GM-CSF had no chemotactic or chemokinetic effect. However, GM-CSF enhanced monocyte transendothelial migration (TEM) through unstimulated and IL-1-activated (5 h) HUVEC in response to C5a or monocyte chemoattractant protein-1 in a dose-dependent fashion, increasing the migration from 28.7 +/- 5.3% to 41.8 +/- 6.2% (n = 8, p < 0.05) and from 34.8 +/- 6% to 50.3 +/- 3.1%, p < 0.05), respectively. The enhanced TEM was inhibited by monoclonal antibodies (mAb) to LFA-1, but not by mAb to Mac-1 or to VLA-4. Furthermore, GM-CSF up-regulated and activated LFA-1, as assessed by NKI-L16 neoepitope expression. The results indicate that: (1) GM-CSF can prime monocytes for increased TEM, (2) GM-CSF enhances LFA-1-mediated monocyte TEM and (3) this effect is in part mediated by increasing LFA-1 expression and activation. Thus, increased GM-CSF production may promote monocyte accumulation in inflammation not only by inducing monocytosis, but also enhancing migration.
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PMID:Enhancement of monocyte transendothelial migration by granulocyte-macrophage colony-stimulating factor: requirement for chemoattractant and CD11a/CD18 mechanisms. 1055 11


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