Chemotaxis of human monocytes by synthetic peptides that mimic segments of <i>Porphyromonas gingivalis</i> fimbrial protein

Ogawa, Tomohiko; Ogo, Hideji; Hamada, Shigeyuki

doi:10.1111/j.1399-302x.1994.tb00068.x

Cited by 20 publications

(10 citation statements)

References 21 publications

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“…5), suggesting either incomplete blocking or that fimbriae activate CD11b–CD18 through an additional pathway. Others have shown that P. gingivalis fimbriae induce chemotaxis of human monocytes in a manner similar to induction by FMLP 23. The FMLP induces chemotaxis or integrin activation by interacting with the G‐protein‐coupled formyl peptide receptor (FPR) 18.…”

Section: Resultsmentioning

confidence: 99%

Integrin activation by bacterial fimbriae through a pathway involving CD14, Toll‐like receptor 2, and phosphatidylinositol‐3‐kinase

2005

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CD11b–CD18 and other integrins play important roles in immunity and inflammation and require prior activation through inside‐out signaling to efficiently bind their ligands. We present evidence for a novel TLR2‐dependent signaling pathway that leads to CD11b–CD18 activation in human monocytes or neutrophils upon recognition of Porphyromonas gingivalis fimbriae through CD14. The activated binding‐state of CD11b–CD18, which involves induction of conformational changes, was monitored through detection of an activation‐specific epitope of CD11b. The ability of fimbriae to induce this activation epitope was significantly inhibited by a mAb to TLR2, but not to TLR4 or unrelated surface molecules. Moreover, the ability of fimbriae to activate CD11b–CD18 was significantly inhibited by pharmacological inhibitors of phosphatidylinositol‐3‐kinase but not of PKC or of p38 mitogen‐activated protein kinase. The signaling pathway activated by fimbriae is distinct from that which is activated by N‐formyl‐Met–Leu–Phe, a prototypical integrin activator, since the former was insensitive to pertussis toxin. This novel function of TLR2 as a signaling receptor for pathogen‐induced activation of CD11b–CD18 may play a significant role in infection‐driven chronic inflammatory conditions, such as periodontal disease or atherosclerosis, where P. gingivalis has been implicated.

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Section: Resultsmentioning

confidence: 99%

Integrin activation by bacterial fimbriae through a pathway involving CD14, Toll‐like receptor 2, and phosphatidylinositol‐3‐kinase

2005

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“…Protein kinase C also mediates LPSengendered production of IL-1, TNF-␣, and nitric oxide from macrophages (235). Both LPS and fimbriae are directly chemotactic for monocytes (180,182). The fimbrial consensus sequence LTxxLTxxN (also involved in cytokine stimulation [see above and Fig.…”

Section: Encounter With Host Defense Mechanismsmentioning

confidence: 99%

Life Below the Gum Line: Pathogenic Mechanisms ofPorphyromonas gingivalis

Lamont

Jenkinson

1998

Microbiol Mol Biol Rev

915

583

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SUMMARY Porphyromonas gingivalis, a gram-negative anaerobe, is a major etiological agent in the initiation and progression of severe forms of periodontal disease. An opportunistic pathogen, P. gingivalis can also exist in commensal harmony with the host, with disease episodes ensuing from a shift in the ecological balance within the complex periodontal microenvironment. Colonization of the subgingival region is facilitated by the ability to adhere to available substrates such as adsorbed salivary molecules, matrix proteins, epithelial cells, and bacteria that are already established as a biofilm on tooth and epithelial surfaces. Binding to all of these substrates may be mediated by various regions of P. gingivalis fimbrillin, the structural subunit of the major fimbriae. P. gingivalis is an asaccharolytic organism, with a requirement for hemin (as a source of iron) and peptides for growth. At least three hemagglutinins and five proteinases are produced to satisfy these requirements. The hemagglutinin and proteinase genes contain extensive regions of highly conserved sequences, with posttranslational processing of proteinase gene products contributing to the formation of multimeric surface protein-adhesin complexes. Many of the virulence properties of P. gingivalis appear to be consequent to its adaptations to obtain hemin and peptides. Thus, hemagglutinins participate in adherence interactions with host cells, while proteinases contribute to inactivation of the effector molecules of the immune response and to tissue destruction. In addition to direct assault on the periodontal tissues, P. gingivalis can modulate eucaryotic cell signal transduction pathways, directing its uptake by gingival epithelial cells. Within this privileged site, P. gingivalis can replicate and impinge upon components of the innate host defense. Although a variety of surface molecules stimulate production of cytokines and other participants in the immune response, P. gingivalis may also undertake a stealth role whereby pivotal immune mediators are selectively inactivated. In keeping with its strict metabolic requirements, regulation of gene expression in P. gingivalis can be controlled at the transcriptional level. Finally, although periodontal disease is localized to the tissues surrounding the tooth, evidence is accumulating that infection with P. gingivalis may predispose to more serious systemic conditions such as cardiovascular disease and to delivery of preterm infants.

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“…Jiang et al (15) demonstrated that oral microorganisms, including P gingivalis, stimulated the production of monocyte chemoattractant protein 1 from mononuclear cells. Ogawa et al (17) demonstrated that P gingivalis fimbrial protein stimulated monocyte migration. Therefore, the organism carrying the fimbriae may be involved in the infiltration of monocytes/macrophages into the inflammatory site.…”

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confidence: 99%

Porphyromonas gingivalis Fimbriae Induce Adhesion of Monocytic Cell Line U937 to Endothelial Cells

Hirose

Isogai

Ueda

2000

Microbiology and Immunology

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This study used the human monocytic cell line U937 to examine whether or not Porphyromonas gingivalis fimbriae could induce the adhesion of monocytes to endothelial cells. An in vitro adhesion assay was used to investigate the effects of the fimbriae on U937 cell adhesion to human umbilical vein endothelial cells (HUVEC). The fimbriae enhanced U937 cell adhesion to HUVEC in a dose-dependent manner. U937 cells adhered better to HUVEC pretreated with the fimbriae for a minimum of 2 hr than to untreated HUVEC. The enhanced adhesion was inhibited by a monoclonal antibody against P gingivalis 381 fimbriae. Pretreatment of U937 cells with the fimbriae for 24 hr enhanced U937 cell adhesion to HUVEC approximately 4-fold. This phenomenon was inhibited by an anti-CD11b antibody, suggesting the involvement of CD11b. These results indicate that P gingivalis fimbriae can induce monocyte adhesion to the endothelial cell surface. They also suggest that the fimbriae may be involved in the initial event for infiltration of monocytes into the periodontal tissues of individuals with adult periodontitis.

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Chemotaxis of human monocytes by synthetic peptides that mimic segments of Porphyromonas gingivalis fimbrial protein

Cited by 20 publications

References 21 publications

Integrin activation by bacterial fimbriae through a pathway involving CD14, Toll‐like receptor 2, and phosphatidylinositol‐3‐kinase

Integrin activation by bacterial fimbriae through a pathway involving CD14, Toll‐like receptor 2, and phosphatidylinositol‐3‐kinase

Life Below the Gum Line: Pathogenic Mechanisms ofPorphyromonas gingivalis

Porphyromonas gingivalis Fimbriae Induce Adhesion of Monocytic Cell Line U937 to Endothelial Cells

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