Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Thiele, D.L. et al.

Regulation of cellular function by products of lysosomal enzyme activity: elimination of human natural killer cells by a dipeptide methyl ester generated from L-leucine methyl ester by monocytes or polymorphonuclear leukocytes.

L-Leucine methyl ester (Leu-OMe) is a lysosomotropic compound that irreversibly removes natural killer cell (NK) function from human peripheral blood mononuclear cells. This effect was dependent on the presence of mononuclear phagocytes (M phi) or polymorphonuclear leukocytes (PMN) and was prevented by lysosomal inhibitors such as chloroquine or NH4Cl. When M phi or PMN were incubated with Leu-OMe, a product was formed that eliminated all NK function from mixed lymphocyte populations. This effect did not require the presence of M phi or PMN and was not prevented by lysosomal enzyme inhibitors. Thin-layer chromatography and mass spectral analysis revealed that this NK-toxic product was L-leucyl-L-leucine methyl ester (Leu-Leu-OMe). When human lymphocytes were exposed to greater than 50 microM Leu-Leu-OMe for 15 min, all NK function was irreversibly eliminated. Other dipeptide methyl esters containing nonpolar L amino acids caused similar effects, but substitution with amino acids containing polar or charged side chains or with D stereoisomers produced compounds that had no toxic effect on NK. These findings indicate that M phi and PMN can regulate NK function by releasing the dipeptide condensation product Leu-Leu-OMe generated from Leu-OMe via a lysosomally mediated mechanism. The data show that specific products of lysosomal enzyme activity may have potent effects on the function of adjacent cells.[1]

References

Regulation of cellular function by products of lysosomal enzyme activity: elimination of human natural killer cells by a dipeptide methyl ester generated from L-leucine methyl ester by monocytes or polymorphonuclear leukocytes. Thiele, D.L., Lipsky, P.E. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.