High Mobility Group Box Chromosomal Protein 1 (HMGB1) Is an Antibacterial Factor Produced by the Human Adenoid

Abstract

Antibacterial factors were purified from human adenoid glands by tissue extraction and consecutive steps of reversedphase chromatography and assayed for bactericidal activity against the airway pathogen Moraxella catarrhalis and also Escherichia coli and Bacillus megaterium. One of the most active components isolated from adenoids was identified by N-terminal sequence analysis and mass spectrometry as high mobility group box chromosomal protein 1 (HMGB1). This novel finding was further substantiated by Western blot analysis, demonstrating a protein of expected size reactive with HMGB1 antiserum. Local synthesis was confirmed by reversetranscriptase PCR and in situ hybridization. Adenoid-derived HMGB1 and recombinant HMGB1 revealed comparable antibacterial activity at high rate. More than 95% of bacteria were eradicated within 5 min by HMGB1 in the cultures. Secretion from the adenoid gland surface was also demonstrated to contain antibacterial activity, mainly mediated by ␣-defensins, but not by HMGB1. We conclude that HMGB1, produced and stored intracellularly in the adenoid gland, contributes to the local antibacterial barrier defense system in the upper respiratory tract. Innate immunity refers to the part of the eukaryotic antimicrobial defense machinery that acts and kills invaders within seconds or minutes. The main effector molecules in this system are gene-derived antimicrobial peptides (peptide antibiotics), and this applies both to plants and animals, including invertebrates and vertebrates (1, 2). More than 500 antimicrobial peptides have been described to date, of which only 30 have been identified in humans (3). Of these, some are small peptides such as defensins and some are well-characterized larger proteins such as lysozyme, phospholipase A 2 , and bactericidal permeability increasing protein, contained in neutrophil granules. Another group consists of cleaved fragments of larger proteins such as lactoferrin and cathepsin G.It was recently reported that nasal secretion contains antimicrobial activity (4) and that the oral mucosa and salivary glands produce ␤-defensins (5). The adenoid or pharyngeal tonsil is a part of the mucosa-associated lymphatic tissue responsible for regional immune functions in the upper respiratory tract. The adenoid has been investigated for production

The gesture life of high mobility group box 1

“…It may also be a key signal for eliciting immune responses to cellular injury and death (Table 1) [34]. The proinflammatory effects of HMGB1, and its critical role in animal models of systemic inflammation, suggest that the protein may be an important therapeutic target for diseases of cytokine excess, including sepsis.…”

“…Nerve growth [8,9,15] Systemic toxicity (H. Yang et al, in preparation) [18,26,28] Increased local host defense [22] Intestinal barrier dysfunction [25 . . ] Antibacterial [34] Tumor metastasis [14,16] …”

Mice Lacking the Lectin-Like Domain of Thrombomodulin Are Protected Against Melioidosis

“…The lectin-like domain of TM is capable of sequestering HMGB1, thereby dampening the proinflammatory properties of HMGB1 (9). We hypothesized that lack of the lectinlike domain would result in increased HMGB1 levels, which on one hand could exert antibacterial effects (34) and on the other hand could exaggerate collateral organ damage. However, HMGB1 levels in BALF of TM LeD/LeD mice were lower than those in BALF of WT mice, most likely as a consequence of the lower bacterial loads in the former group, inducing a less severe proinflammatory response.…”

Bedeutung der angeborenen Immunantwort in der Sepsis

“…Eine Rezeptor-unabhängige Wirkung ist die kürzliche Entdeckung bakterizider Eigenschaften von HMGB1. Seitdem kann HMGB1 auch zur Gruppe der antimikrobiellen Peptide gezählt werden [205].…”