Alpha 2-macroglobulin functions as a cytokine carrier to induce nitric oxide synthesis and cause nitric oxide-dependent cytotoxicity in the RAW 264.7 macrophage cell line.

The Journal of Biological Chemistry
J J LysiakS L Gonias

Abstract

Nitric oxide (NO) is an important mediator of macrophage activities. We studied the regulation of macrophage NO synthesis by alpha 2-macroglobulin (alpha 2M), a proteinase inhibitor and carrier of certain growth factors, including transforming growth factor-beta (TGF-beta). Native alpha 2M and the alpha 2M receptor-recognized derivative, alpha 2M-methylamine (alpha 2M-MA), increased nitrite generation by the RAW 264.7 murine macrophage cell line. The level of nitrite accumulation, which is an index of NO synthesis, was comparable to that observed with interferon-gamma. Native alpha 2M and alpha 2M-MA also increased inducible nitric oxide synthase (iNOS) mRNA levels and substantially reduced the number of viable cells, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium/succiny l dehydrogenase assay or trypan blue exclusion. At slightly higher alpha 2M concentrations, [3H]thymidine incorporation was inhibited. All of these activities were counteracted nearly completely when the iNOS competitive inhibitor NG-monomethyl-L-arginine was included. By in situ nick translation, native alpha 2M and alpha 2M-MA increased the percentage of cells with detectable single strand chromatin nicks from 4 to 12 and 17%, respecti...Continue Reading

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Citations

May 24, 2008·The Journal of Biological Chemistry·Elisabetta MantuanoSteven L Gonias
Oct 7, 2006·Free Radical Biology & Medicine·Li HuangDouglas Borchman
Nov 10, 2011·Diabetes/metabolism Research and Reviews·Yoon Sin OhHee-Sook Jun
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Dec 31, 2003·The Journal of Biological Chemistry·Ana María SalicioniSteven L Gonias
Nov 13, 2001·Molecular Cell Biology Research Communications : MCBRC·H J Zhu, A W Burgess
Mar 17, 2007·The Journal of Nutritional Biochemistry·Nanmei LiuMaria C Linder

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