IngentaConnect Role of Heme-Hemopexin in Human T-Lymphocyte Proliferation

Abstract:

Heme-hemopexin supports and stimulates proliferation of human acute T-lymphoblastic (MOLT-3) cells, suggesting the participation of heme in cell growth and division. MOLT-3 cells express approximately 58,000 hemopexin receptors per cell (apparent K d 20 n M ), of which about 20% are on the cell surface. Binding is dose- and temperature-dependent, and growth in serum-free IMDM medium is stimulated by 100-1000 n M heme-hemopexin, consistent with the high affinity of the receptor for hemopexin, and maximal growth is seen in response to 500 n M complex. Growth was similar in defined minimal medium supplemented with either low concentrations of heme-hemopexin or iron-transferrin, and either of these complexes were about 80% as effective as a serum supplement. Heme-hemopexin, but not apo-hemopexin, reversed the growth inhibition caused by desferrioxamine showing that heme-iron derived from heme catabolism is used for cell growth. Cobalt-protoporphyrin (CoPP)-hemopexin, which binds to the receptor but is not transported intracellularly [Smith et al., (1993) J. Biol. Chem. 268, 7365], also stimulated cell proliferation in serum-free IMDM but did not "rescue" the cells from desferrioxamine. Furthermore, CoPP-hemopexin effectively competed for the hemopexin receptor with heme-hemopexin and diminished its growth stimulatory effects. In addition, protein kinase C (PKC) is translocated to the plasma membrane within 5 min after heme-hemopexin is added to the medium, reaches maximum activity within 5-10 min, and declines to unstimulated levels by 30 min. Heme-hemopexin and CoPP-hemopexin both augmented MOLT-3 cell growth stimulated by serum. Thus, heme-hemopexin not only functions as an iron source for T-cells but occupancy of the hemopexin receptor itself triggers signaling pathway(s) involved in the regulation of cell growth. The stimulation of growth of human T-lymphocytes by heme-hemopexin is likely to be a physiologically relevant mechanism at sites of injury, infection, and inflammation.

Language: English

Document Type: Research article

Affiliations: 1: School of Biological Sciences, University of Missouri-Kansas City, 5100 Rockhill Road, Kansas City, Missouri, 64110-2499 2: Department of Microbiology and Immunology, University of South Carolina Medical School, Columbia, South Carolina, 29208

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