Identification of a Natural Killer Enhancing Factor (NKEF) from Human Erythroid Cells

Structure, organization and expression of common carp (Cyprinus carpio L.) NKEF-B gene

“…Teleost NKEF-A/B function remains to be further investigated. By the experiments with NK assay, Shau et al demonstrated that RBC increased NK cytotoxicity [5]. Further, by ELISA, Western blot analysis, and immunohistological staining with antibodies against NKEF, they demonstrated that the protein is expressed by the exquisitely NK-sensitive human erythroleukemic cell line K562, which was later found to express characteristics of erythroid lineage [4].…”

“…It is important to note that the NKEF-B positive cells are mainly some RBCs and a few epithelial cells in gill and intestine, suggesting that these positive cells were likely to be NKEF-B producing cells and related to innate immune function/antioxidant activity of teleosts, and that in SVCV-infected carp, these positive cells or positive products in cytoplasm were obviously increased in gill and spleen tissue sections compared to control carp, which is basically consistent with the results of the real-time RT-PCR analysis as described above. Although in human, the sensitive cell lines of NKEF-A and B may be the K562 and the endothelial cell line ECV304 respectively [4,5], we think that the reason why the NKEF-B positive cells were found in some RBCs of carp may be as follows: 1) several clones, referred to NKEF-A and B genes, were isolated from a lgt11 cDNA library of K562 [4], suggesting that the RBCs can express NKEF-B gene; additionally, porcine NKEF-B was purified from the cytosol of RBCs [8]; given the fact that large amount of hydrogen peroxide and other reactive oxygen species are constantly generated in RBCs, it would not be surprising that the peptide coded by NKEF-B is involved in coping with oxidative stress in RBCs [4]; 2) by the cross reaction with a rabbit polyclonal antibody for carp rNKEF-B, there may be some NKEF-A positive cells among the detected NKEF-B positive RBCs.…”

“…NK cell enhancing factor (NKEF) was originally cloned from human red blood cells (RBCs) as a soluble factor that enhance NK cytotoxicity against tumor cells in vitro [5]. NKEF belongs to a new class of highly conserved peroxiredoxin gene family (Prx, containing six members) found in various organisms from prokaryotes to mammals [4].…”

Peroxiredoxin 1 – an antioxidant enzyme in cancer

“…Upon peroxidatic Cys oxidation, 2‐Cys PRDX1 is structurally converted from a peroxidase enzyme to a molecular chaperone under stress conditions 9, 10. In addition to its peroxidase and chaperone functions, PRDX1 could also enhance natural killer cell cytotoxicity and suppress oncogenic proteins such as c‐Myc and c‐Abl 11, 12, 13. Recent studies have shown that abnormal expression of PRDX1 has been observed in several human cancers, including breast, oesophageal, lung and prostate cancers 14, 15, 16, 17.…”

Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression

“…Transfection studies show that Prdx1 can eliminate peroxide in vivo and can regulate ROS induced by growth factor signalling 9 . In addition to its role as an antioxidant enzyme, Prdx1 has been independently isolated as an erythrocyte cytosolic protein that enhances the cytoxicity of natural killer (NK) cells 10 , a Figure 1 Premature death in ageing Prdx1 2/2 mice. a, Genotype of four littermates from a Prdx1 þ/2 cross.…”