A novel role for β2-microglobulin: a precursor of antibacterial chemokine in respiratory epithelial cells

Abstract

We analyzed a panel of cationic molecules secreted in the culture medium of human respiratory epithelial cells (REC) upon activation by IL-1β and different pathogen-associated molecular patterns. A 9 kDa fragment derived from β2-microglobulin (B2M) was identified and named shed 9 kDa B2M (sB2M-9). The primary structure of sB2M-9 was revealed to increase its pI value that potentially could play an important role in innate defense. sB2M-9 exhibits antibacterial activity against Gram positive Staphylococcus aureus (SA) but not against Gram negative Klebsiella pneumonia (KP). Upon its binding to SA, sB2M-9 induces clumps, a phenomenon not observed with B2M. Migration of THP-1 monocytes exposed to SA clumps was significantly greater than that to SA without clumps. sB2M-9 binds to SA, more likely as a chemokine, to facilitate THP-1 migration. As a whole, we demonstrated that REC release a novel chemokine with antibacterial activity that is shed from B2M to facilitate THP-1 migration.

Genetic mechanisms regulating the host response during mastitis

“…The B2M protein is classically known for its noncovalent association with class I BoLA, which present endogenous antigens associated with cancerous cells and viral-infected cell CD8+ T-lymphocytes that subsequently kill the cell (Behl et al, 2012). More recently, a 9-kD fragment of B2M was shown to possess antibacterial activity against S. aureus, and may function as a monocyte chemoattractant (Chiou et al, 2016). In beef cattle, 12 mutations in the B2M gene were associated with changes in milk protein and IgG, which led to an elevated SCC (Clawson et al, 2004;Sanchez et al, 2004).…”

WITHDRAWN: Knockout of β2 Microglobulin Potentiates The Effects of IFN-γ Priming On The Survival and Immunomodulatory Capacities of Mesenchymal Stem Cells

“…Moreover, B2M-knockout MSCs also secreted similar or less levels of proin ammatory cytokines even when exposed to IFN-γ, and further studies are needed to de ne the underlying mechanism of this phenomenon. β2-microglobulin exists as a secretory form not just constituting MHC class I and may have various unknown functions, given that it also interacts with immune cells and even functions as a chemokine [37][38][39]. We speculated that the lack of β2microglobulin would not likely have adverse effects on in ammation considering that a high level of this protein is associated with the severity of in ammatory disorders such as in ammatory bowel disease, systemic lupus erythematosus and ankylosing spondylitis [39][40][41].…”

Respiratory ß-2-Microglobulin exerts pH dependent antimicrobial activity

“…In BAL fluid of healthy adults, it reaches concentrations of 0.08 mg/l with higher concentrations observed in children [ 43 ], while serum concentrations of B2M range between 1 and 3 mg/l [ 20 ]. A large fragment of B2M has also been detected in the culture supernatant of respiratory epithelial cells upon stimulation with IL-1ß [ 24 ]. It was shown to generate aggregates of S. aureus , facilitating the phagocytosis of clusters of bacteria by THP-1 cells.…”

“…B2M shows activity against L. monocytogenes, Staphylococcus aureus, Proteus vulgaris, and Escherichia coli [ 17 ]. Furthermore, the peptide is the precursor of a fragment secreted from human respiratory epithelial cells which serves as chemoattractant for THP-1 monocytes, thus enhancing phagocytosis of Staphylococcus aureus [ 24 ]. A reported dose-dependent upregulation of B2M mRNA and secretion of B2M upon stimulation of amniotic cells with bacterial lipopolysaccharide further supports the hypothesis of the antibacterial peptide function [ 17 ].…”