Calprotectin Expression Inhibits Bacterial Binding to Mucosal Epithelial Cells

Nisapakultorn, Kanokwan; Ross, Kristin; Herzberg, Mark C.

doi:10.1128/iai.69.6.3692-3696.2001

Cited by 88 publications

(72 citation statements)

References 34 publications

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“…Furthermore, the proteins bind arachidonic acid, and depletion of arachidonic acid has also been suggested as a mechanism of bacterial growth inhibition (49,50). Observations suggesting that S100A8/A9 contributes to mucosal innate immunity are that the complex inhibits invasion of epithelial cells by bacterial pathogens (51), and a recent study showing that S100A9 is crucial for keratinocyte resistance to invasion by Listeria monocytogenes and Salmonella typhimurium (52). In the present study, we provide evidence for another and more direct antibacterial mechanism.…”

Section: Discussionsupporting

confidence: 62%

Bacterial Surface Protein L Binds and Inactivates Neutrophil Proteins S100A8/A9

Åkerström

Björck

2009

The Journal of Immunology

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Finegoldia magna is an anaerobic bacterial species that is part of the normal human flora on all nonsterile body surfaces, but it is also a significant opportunistic pathogen causing a wide range of infections. Some isolates of F. magna that are more frequently associated with clinical infection express protein L, a surface protein containing multiple homologous domains (B1-B5) that bind Igs through interactions with Ig L chains. The present study shows that the N-terminal A domain of protein L binds S100A8/A9, antibacterial proteins present in large amounts in the cytoplasm of neutrophils, but also extracellularly in tissues during inflammation. As a result, protein L-expressing F. magna are protected against killing by S100A8/A9. Igs and S100A8/A9 were found to interact independently with protein L, demonstrating that this bacterial surface protein is capable of manipulating both adaptive and innate immune defense mechanisms.

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Section: Discussionsupporting

confidence: 62%

Bacterial Surface Protein L Binds and Inactivates Neutrophil Proteins S100A8/A9

Åkerström

Björck

2009

The Journal of Immunology

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“…As described previously (21), the monolayers were infected with L. monocytogenes for 2 h at an m.o.i. of 100:1, washed twice with Dulbecco's PBS, and fixed with 4% paraformaldehyde.…”

Section: Methodsmentioning

confidence: 99%

“…Calprotectin also inhibits bacterial invasion of epithelial cells by Listeria monocytogenes, S. typhimurium, and Porphyromonas gingivalis (20,21). By promoting resistance to bacterial invasion, calprotectin-expressing cells, including squamous oral keratinocytes, are likely to contribute to mucosal innate immunity.…”

mentioning

confidence: 99%

Calprotectin S100A9 Calcium-binding Loops I and II Are Essential for Keratinocyte Resistance to Bacterial Invasion

Champaiboon

Sappington

Guenther

et al. 2009

Journal of Biological Chemistry

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Epithelial cells expressing calprotectin, a heterodimer of S100A8 and S100A9 proteins, are more resistant to bacterial invasion. To determine structural motifs that affect resistance to bacterial invasion, mutations were constructed in S100A9 targeting the calcium-binding loops I and II (E36Q, E78Q, E36Q,E78Q) and the C terminus (S100A9 1-99 and S100A9 1-112 ), which contains putative antimicrobial zinc-binding and phosphorylation sites. The S100A8 and mutated S100A9 encoding plasmids were transfected into calprotectin-negative KB carcinoma cells. All transfected cells (except KB-sham) expressed 27E10-reactive heterodimers. In bacterial invasion assays with Listeria monocytogenes and Salmonella enterica serovar Typhimurium (Salmonella typhimurium), cell lines expressing S100A8 in complex with S100A9 E36Q , S100A9 E78Q , S100A9 1-99 , or S100A9 1-112 mutants or the S100A9 1-114 (full-length) calprotectin resisted bacterial invasion better than KB-sham. When compared with KB-S100A8/A9 1-114 , cells expressing truncated S100A9 1-99 or S100A9 1-112 with S100A8 also showed increased resistance to bacterial invasion. In contrast, glutamic acid residues 36 and 78 in calcium-binding loops I and II promote resistance in epithelial cells, because cells expressing S100A9 E36Q,E78Q with S100A8 were unable to resist bacterial invasion. Mutations in S100A9 E36Q, E78Q were predicted to cause loss of the calcium-induced positive face in calprotectin, reducing interactions with microtubules and appearing to be crucial for keratinocyte resistance to bacterial invasion.

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“…Together, these activities indicate a putative role in regulating leukocyte migration to inflammatory sites. S100A8/A9 is also known to inhibit microbial growth, presumably by chelating zinc (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) and to inhibit bacterial adhesion to mucosal epithelial cells (34). Thus, it is reasonable to propose a role in innate immune responses to bacterial infections for these molecules.…”

mentioning

confidence: 99%

Blockade of S100A8 and S100A9 Suppresses Neutrophil Migration in Response to Lipopolysaccharide

Vandal

Rouleau

Boivin

et al. 2003

The Journal of Immunology

200

169

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Recently, proinflammatory activities had been described for S100A8 and S100A9, two proteins found at inflammatory sites and within the neutrophil cytoplasm. In this study, we investigated the role of these proteins in neutrophil migration in vivo in response to LPS. LPS was injected into the murine air pouch, which led to the release of S100A8, S100A9, and S100A8/A9 in the pouch exudates that preceded accumulation of neutrophils. Passive immunization against S100A8 and S100A9 led to a 52% inhibition of neutrophil migration in response to LPS at 3 h postinjection. Injection of LPS was also associated with an increase in peripheral blood neutrophils and the presence in serum of S100A9 and S100A8/A9. Intravenous injection of S100A8, S100A9, or S100A8/A9 augmented the number of circulating neutrophils and diminished the number of neutrophils in the bone marrow, demonstrating that S100A8 and S100A9 induced the mobilization of neutrophils from the bone marrow to the blood. Finally, passive immunization with anti-S100A9 inhibited the neutrophilia associated with LPS injection in the air pouch. These results suggest that S100A8 and S100A9 play a role in the inflammatory response to LPS by inducing the release of neutrophils from the bone marrow and directing their migration to the inflammatory site.

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Calprotectin Expression Inhibits Bacterial Binding to Mucosal Epithelial Cells

Cited by 88 publications

References 34 publications

Bacterial Surface Protein L Binds and Inactivates Neutrophil Proteins S100A8/A9

Bacterial Surface Protein L Binds and Inactivates Neutrophil Proteins S100A8/A9

Calprotectin S100A9 Calcium-binding Loops I and II Are Essential for Keratinocyte Resistance to Bacterial Invasion

Blockade of S100A8 and S100A9 Suppresses Neutrophil Migration in Response to Lipopolysaccharide

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