HMGN2: a novel antimicrobial effector molecule of human mononuclear leukocytes?

Abstract

Leukocytes are a central cellular element of innate-immune defense in mammals. In addition to the generation of toxic oxygen radicals and nitric oxide, leukocytes express and secrete a broad array of antimicrobial proteins and peptides. In the study, an antimicrobial polypeptide was isolated and purified from human peripheral blood mononuclear leukocytes in the presence of interleukin (IL)-2. Microsequencing provided that its N-terminal amino sequence was PKRKAEGDAK, which was identical to high mobility group nucleosomal-binding domain 2 (HMGN2). Mass spectrometric value and Western blot also indicated its individual character of HMGN2. The antimicrobial assays showed that the Escherichia coli-based production of HMGN2 had a potent antimicrobial activity against E. coli ML-35p, Pseudomonas aeruginosa ATCC 27853, and to some extent, against Candida albicans ATCC 10231. The HMGN2 alpha-helical domain had the same antimicrobial activity as HMGN2. The immunocytochemistry staining, enzyme-linked immunosorbent assay, and Western blot revealed that HMGN2 was present in the cytoplasm of mononuclear leukocytes and released to the extracellular environment when stimulated with IL-2. These results suggest that HMGN2 would be a novel antimicrobial effector molecule of human mononuclear leukocyte.

High Mobility Group Nucleosomal Binding Domain 2 (HMGN2) SUMOylation by the SUMO E3 Ligase PIAS1 Decreases the Binding Affinity to Nucleosome Core Particles

“…HMGN2 facilitates the ability of DNA repair proteins to access and repair UV-induced DNA lesions in chromatin (8), and is a regulator of homeodomain transcription factor activity modulated by Wnt/␤-catenin signaling (9). HMGN2 has broad spectrum antimicrobial activity against bacteria (10) and promotes lipopolysaccharide (LPS)-induced ␤-defensin expression in epithelial cells (11). In addition, HMGN2 could be released from peripheral blood mononuclear leukocytes after IL-2 treatment (10), although its translocation mechanism has not been elucidated.…”

High-mobility group protein N2 (HMGN2) inhibited the internalization of <italic>Klebsiella pneumoniae</italic> into cultured bladder epithelial cells

“…Series of experiments have shown that HMGN2 is preferentially associated with gene transcription and organogenesis [11]. Recently, our group has isolated an antimicrobial polypeptide from human lympholine-activated killer (LAK) cells and cervical mucus, which is characterized to be the HMGN2 [12,13]. Until now, the biological role of this protein has not been fully defined.…”

“…Until now, the biological role of this protein has not been fully defined. Our previous work has illustrated that the transmembrane a-helical structure located in the 17 -47 residues, which has been found to be the DNA-binding domain of HMGN2, is essential for its antibacterial activity against Escherichia coli ML-35p, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 10231, and, to some extent, against human hepatitis B virus [13,14].…”

High Mobility Group Nucleosomal Binding Domain 2 Protein Protects Bladder Epithelial Cells from Klebsiella pneumoniae Invasion

“…HMGN2 shows potent antimicrobial activity against Escherichia coli ML-35p, Pseudomonas aeruginosa ATCC 27853 and, to some extent, against Candida albicans ATCC 10231. 7,8) HMGN2 protein inhibits hepatic B virus (HBV) protein expression and replication in vitro. 9) HMGN2 also shows anti-cancer potency in HeLa cells.…”