Dataset Information

Differential Enhancement of Neutrophil Phagocytosis by Anti-Bactericidal/Permeability-Increasing Protein Antibodies.

ABSTRACT: Bactericidal/permeability-increasing protein (BPI) plays a major role in innate immunity through the ability of the N-terminal domain (NTD) to bind LPS, mediate cytotoxicity, and block LPS-induced inflammation. The C-terminal domain mediates phagocytosis of bacteria bound to the NTD. These two domains are linked by a surface-exposed loop at amino acids 231-249 for human BPI, known as the "hinge region." Autoantibodies to human BPI are prevalent in many chronic lung diseases; their presence is strongly correlated with Pseudomonas aeruginosa and with worse lung function in patients with cystic fibrosis and bronchiectasis. Although prior literature has reported BPI neutralization effect with autoantibodies targeting either NTD or C-terminal domain, the functionality of BPI Ab to the hinge region has never been investigated. Here, we report that Ab responses to the BPI hinge region mediate a remarkably selective potentiation of BPI-dependent phagocytosis of P. aeruginosa with both human and murine neutrophils in vitro and in vivo. These findings indicate that autoantibodies to the BPI hinge region might enhance bacterial clearance.

SUBMITTER: Theprungsirikul J

PROVIDER: S-EPMC8354091 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

Differential Enhancement of Neutrophil Phagocytosis by Anti-Bactericidal/Permeability-Increasing Protein Antibodies.

Theprungsirikul Jomkuan J Skopelja-Gardner Sladjana S Wierzbicki Rachel M RM Sessions Katherine J KJ Rigby William F C WFC

Journal of immunology (Baltimore, Md. : 1950) 20210716 3

Bactericidal/permeability-increasing protein (BPI) plays a major role in innate immunity through the ability of the N-terminal domain (NTD) to bind LPS, mediate cytotoxicity, and block LPS-induced inflammation. The C-terminal domain mediates phagocytosis of bacteria bound to the NTD. These two domains are linked by a surface-exposed loop at amino acids 231-249 for human BPI, known as the "hinge region." Autoantibodies to human BPI are prevalent in many chronic lung diseases; their presence is st ...[more]

PMID: 34272233

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Project description:BACKGROUND: Cattle and other ruminants have evolved the ability to derive most of their metabolic energy requirement from otherwise indigestible plant matter through a symbiotic relationship with plant fibre degrading microbes within a specialised fermentation chamber, the rumen. The genetic changes underlying the evolution of the ruminant lifestyle are poorly understood. The BPI-like locus encodes several putative innate immune proteins, expressed predominantly in the oral cavity and airways, which are structurally related to Bactericidal/Permeability Increasing protein (BPI). We have previously reported the expression of variant BPI-like proteins in cattle (Biochim Biophys Acta 2002, 1579, 92-100). Characterisation of the BPI-like locus in cattle would lead to a better understanding of the role of the BPI-like proteins in cattle physiology RESULTS: We have sequenced and characterised a 722 kbp segment of BTA13 containing the bovine BPI-like protein locus. Nine of the 13 contiguous BPI-like genes in the locus in cattle are orthologous to genes in the human and mouse locus, and are thought to play a role in host defence. Phylogenetic analysis indicates the remaining four genes, which we have named BSP30A, BSP30B, BSP30C and BSP30D, appear to have arisen in cattle through a series of duplications. The transcripts of the four BSP30 genes are most abundant in tissues associated with the oral cavity and airways. BSP30C transcripts are also found in the abomasum. This, as well as the ratios of non-synonymous to synonymous differences between pairs of the BSP30 genes, is consistent with at least BSP30C having acquired a distinct function from the other BSP30 proteins and from its paralog in human and mouse, parotid secretory protein (PSP). CONCLUSION: The BPI-like locus in mammals appears to have evolved rapidly through multiple gene duplication events, and is thus a hot spot for genome evolution. It is possible that BSP30 gene duplication is a characteristic feature of ruminants and that the BSP30 proteins contribute to an aspect of ruminant-specific physiology.

Dataset Information

Differential Enhancement of Neutrophil Phagocytosis by Anti-Bactericidal/Permeability-Increasing Protein Antibodies.

Publications

Differential Enhancement of Neutrophil Phagocytosis by Anti-Bactericidal/Permeability-Increasing Protein Antibodies.

Similar Datasets

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