Role of heme-hemopexin in human T-lymphocyte proliferation.
Role of heme-hemopexin in human T-lymphocyte proliferation.
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DOI：
10.1006/excr.1997.3526
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发表时间：
1997-05
影响因子：
3.7
通讯作者：
A. Smith;J. Eskew;C. Borza;M. Pendrak;R. Hunt
中科院分区：
文献类型：
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作者：
A. Smith;J. Eskew;C. Borza;M. Pendrak;R. Hunt
血红素血红素结合蛋白支持并刺激人急性T淋巴母细胞（MOLT-3）细胞的增殖，表明血红素参与细胞生长和分裂。MOLT-3细胞每个细胞表达约58，000个血红素结合蛋白受体（表观Kd 20 nM），其中约20%在细胞表面上。结合是剂量和温度依赖性的，并且在无血清IMDM培养基中的生长被100-1000 nM血红素-血红素结合蛋白刺激，这与受体对血红素结合蛋白的高亲和力一致，并且在响应于500 nM复合物时观察到最大生长。生长是相似的，在确定的基本培养基中补充低浓度的血红素血红素结合蛋白或铁转铁蛋白，这些复合物的约80%作为血清补充剂的有效。血红素血红素结合蛋白，但不是脱辅基血红素结合蛋白，逆转由去铁胺引起的生长抑制，表明来自血红素catenorase的血红素铁用于细胞生长。钴-原卟啉（CoPP）-血红素结合蛋白，其与受体结合但不被细胞内转运[Smith等人，（1993）J.Biol.Chem.268，7365]，也刺激无血清IMDM中的细胞增殖，但不能从去铁胺中“拯救”细胞。此外，CoPP-血红素结合蛋白与血红素-血红素结合蛋白有效竞争血红素结合蛋白受体并减弱其生长刺激作用。此外，蛋白激酶C（PKC）被易位到质膜后5分钟内加入到培养基中，在5-10分钟内达到最大活性，并下降到未受刺激的水平，由30分钟。血红素-血红素结合蛋白和铜-血红素结合蛋白都增强MOLT-3细胞生长血清刺激。因此，血红素-血红素结合蛋白不仅用作T细胞的铁源，而且血红素结合蛋白受体本身的占据触发参与细胞生长调节的信号传导途径。血红素-血红素结合蛋白刺激人T淋巴细胞生长可能是损伤、感染和炎症部位的生理相关机制。
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 Kd 20 nM), 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 nM heme-hemopexin, consistent with the high affinity of the receptor for hemopexin, and maximal growth is seen in response to 500 nM 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.