Porphyromonas gingivalis induces murine macrophage foam cell formation

Min, Qi; Miyakawa, Hiroshi; Kuramitsu, Howard K.

doi:10.1016/j.micpath.2003.07.002

Cited by 124 publications

(116 citation statements)

References 38 publications

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“…Previous reports have shown that MVs possess various virulent abilities (9,13,25,39,40,43,48), while our results indicate a new aspect of cellular function impairment by P. gingivalis MVs.…”

Section: Discussionsupporting

confidence: 63%

Entry ofPorphyromonas gingivalisOuter Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment

2009

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Bacteria have evolved mechanisms for the secretion of virulence factors into host cells; these virulence factors alter host cell biology and enable bacterial colonization (11). Bacterial outer membrane vesicles (MVs), ubiquitously shed from gramnegative bacteria by a mechanism involving cell wall turnover, consist of a subset of outer membrane and soluble periplasmic components (54). This extracellular secretion system likely plays a part in the strategy utilized by bacterial pathogens to modulate host defense and response and impair host cell function. For example, Pseudomonas aeruginosa (3), Helicobacter pylori (19), and Actinobacillus actinomycetemcomitans (8), as well as pathogenic and nonpathogenic Escherichia coli (7, 51), secrete MVs that contain toxins, proteases, adhesins, and lipopolysaccharide. Therefore, it has been proposed that MVs are bacterial "bombs" (30). However, the molecular mechanism of MV entry into host cells is unclear, while it also remains unknown whether MV-associated virulence factors have cytotoxic effects within the invaded cells. A recent study showed that enterotoxigenic E. coli MVs containing heat-labile enterotoxin and other bacterial envelope components were taken up by a human epithelial cell line via cellular lipid rafts, after which intracellular MVs accumulated in nonacidified compartments inaccessible to the extracellular milieu (28). In addition, a very recent study found that Pseudomonas aeruginosa MVs deliver multiple virulence factors, including ␤-lactamase, alkaline phosphatase, hemolytic phospholipase C, and Cif (cystic fibrosis transmembrane conductance regulator inhibitory factor), directly into the host cytoplasm via fusion of MVs with lipid rafts in the host plasma membrane, which has an effect on host cell biology (5). Thus, it is likely MVs function as specifically targeted transport vehicles to mediate entry of bacterial virulence factors into host cells. However, no other related results have been reported.Periodontitis, one of the most common infectious diseases seen in humans (52), is characterized by gingival inflammation, as well as loss of connective tissue and bone from around the roots of the teeth, which leads to eventual tooth exfoliation. Porphyromonas gingivalis is considered to be a bona fide pathogen that causes several forms of severe periodontal disease. The bacterium releases MVs in an extracellular manner; these MVs retain the full components of outer membrane constituents, including lipopolysaccharide, muramic acid, a capsule, fimbriae, and proteases termed gingipains (13,35). Fimbriae reportedly mediate bacterial adherence to and entry into periodontal cells (2), while gingipains, which consist of arginine (Arg-gingipain [Rgp])-and lysine (Lys-gingipain [Kgp])-specific cysteine proteinases, contribute to the destruction of periodontal tissues (24). Gingipains degrade collagen and fibronectin and inhibit interactions between host cells and the extracellular matrix. In addition, they degrade various cytokines, resulting in a disturbance of t...

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Section: Discussionsupporting

confidence: 63%

Entry ofPorphyromonas gingivalisOuter Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment

2009

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“…In addition, MVs have been reported to possess various virulent abilities (9,13,21,39,41,47,51). We intend to conduct additional studies to elucidate the cellular functions impaired by invading MVs.…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis Outer Membrane Vesicles Enter Human Epithelial Cells via an Endocytic Pathway and Are Sorted to Lysosomal Compartments

et al. 2009

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Porphyromonas gingivalis, a periodontal pathogen, secretes outer membrane vesicles (MVs) that contain major virulence factors, including major fimbriae and proteases termed gingipains, although it is not confirmed whether MVs enter host cells. In this study, we analyzed the mechanisms involved in the interactions of P. gingivalis MVs with human epithelial cells. Our results showed that MVs swiftly adhered to HeLa and immortalized human gingival epithelial cells in a fimbria-dependent manner and then entered via a lipid raft-dependent endocytic pathway. The intracellular MVs were subsequently routed to early endosome antigen 1-associated compartments and then were sorted to lysosomal compartments within 90 min, suggesting that intracellular MVs were ultimately degraded by the cellular digestive machinery. However, P. gingivalis MVs remained there for over 24 h and significantly induced acidified compartment formation after being taken up by the cellular digestive machinery. In addition, MV entry was shown to be mediated by a novel pathway for transmission of bacterial products into host cells, a Rac1-regulated pinocytic pathway that is independent of caveolin, dynamin, and clathrin. Our findings indicate that P. gingivalis MVs efficiently enter host cells via an endocytic pathway and survive within the endocyte organelles for an extended period, which provides better understanding of the role of MVs in the etiology of periodontitis.

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“…They enter the walls of arteries where they initiate local inflammation associated with early stages of atherosclerosis. 104 Qi et al 105 reported that vesicles and LPS, released by P. gingivalis, activate macrophages to form foam cells, which are important mediators of the cascade of pathological events occurring in atherosclerosis.…”

Section: Bacterial Microvesicles In Periodontitis and Associated Athementioning

confidence: 99%

Role of extracellular membrane vesicles in the pathogenesis of various diseases, including cancer, renal diseases, atherosclerosis, and arthritis

Anderson

Mulhall

Garimella

2010

Laboratory Investigation

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Porphyromonas gingivalis induces murine macrophage foam cell formation

Cited by 124 publications

References 38 publications

Entry ofPorphyromonas gingivalisOuter Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment

Entry ofPorphyromonas gingivalisOuter Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment

Porphyromonas gingivalis Outer Membrane Vesicles Enter Human Epithelial Cells via an Endocytic Pathway and Are Sorted to Lysosomal Compartments

Role of extracellular membrane vesicles in the pathogenesis of various diseases, including cancer, renal diseases, atherosclerosis, and arthritis

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