Lipoxin A4 Analogues Inhibit Leukocyte Recruitment to Porphyromonas gingivalis: A Role for Cyclooxygenase-2 and Lipoxins in Periodontal Disease

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• 作者：Marc Pouliot ; Clary B. Clish ; Nicos A. Petasis ; Thomas E. Van Dyke ; and Charles N. Serhan
• 刊名：Biochemistry
• 出版年：2000
• 出版时间：April 25, 2000
• 年：2000
• 卷：39
• 期：16
• 页码：4761 - 4768
• 全文大小：169K
• 年卷期：v.39,no.16(April 25, 2000)
• ISSN：1520-4995

文摘

The potential involvement of the inducible cyclooxygenase isoform (COX-2) and the role ofnovel lipid mediators were investigated in the pathogenesis of periodontal disease. Crevicular fluids fromlocalized juvenile periodontitis (LJP) patients contained prostaglandin (PG)E₂ and 5-lipoxygenase-derivedproducts, leukotriene B₄, and the biosynthesis interaction product, lipoxin (LX)A₄. Neutrophils fromperipheral blood of LJP patients, but not from asymptomatic donors, also generated LXA₄, suggesting arole for this immunomodulatory molecule in periodontal disease. To characterize host responses of interestto periodontal pathogens, Porphyromonas gingivalis was introduced within murine dorsal air pouches. Inthe air pouch cavity, P. gingivalis elicited leukocyte infiltration, concomitant with elevated PGE₂ levelsin the cellular exudates, and upregulated COX-2 expression in infiltrated leukocytes. In addition, humanneutrophils exposed to P. gingivalis also upregulated COX-2 expression. Blood borne P. gingivalis gavesignificant increases in the murine tissue levels of COX-2 mRNA associated with both heart and lungs,supporting a potential role for this oral pathogen in the evolution of systemic events. The administrationof metabolically stable analogues of LX and of aspirin-triggered LX potently blocked neutrophil trafficinto the dorsal pouch cavity and lowered PGE₂ levels within exudates. Together, these results identifyPMN as an additional and potentially important source of PGE₂ in periodontal tissues. Moreover, theyprovide evidence for a novel protective role for LX in periodontitis, limiting further PMN recruitmentand PMN-mediated tissue injury that can lead to loss of inflammatory barriers that prevent systemictissue invasion of oral microbial pathogens.