Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 μM) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A4. Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1–100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression.
References
[1]
Van Dyke TE, Serhan CN (2003) Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. J Dent Res 82: 82–90.
[2]
The J, Ebersole JL (1991) Rheumatoid factor (RF) distribution in periodontal disease. Journal of Clinical Immunology 11: 132–142.
[3]
Boggess KA, Lieff S, Murtha AP, Moss K, Beck J, et al. (2003) Maternal periodontal disease is associated with an increased risk for preeclampsia. Obstetrics and Gynecology 101: 227–231.
[4]
Offenbacher S, Boggess KA, Murtha AP, Jared HL, Lieff S, et al. (2006) Progressive periodontal disease and risk of very preterm delivery. Obstetrics and Gynecology 107: 29–36.
[5]
Taylor GW, Burt BA, Becker MP, Genco RJ, Shlossman M, et al. (1996) Severe periodontitis and risk for poor glycemic control in patients with non-insulin-dependent diabetes mellitus. Journal of Periodontology 67: 1085–1093.
[6]
Friedewald VE, Kornman KS, Beck JD, Genco R, Goldfine A, et al. (2009) The American Journal of Cardiology and Journal of Periodontology editors' consensus: periodontitis and atherosclerotic cardiovascular disease. Journal of Periodontology 80: 1021–1032.
[7]
Page RC, Eke PI (2007) Case definitions for use in population-based surveillance of periodontitis. Journal of Periodontology 78: 1387–1399.
[8]
Hasturk H, Kantarci A, Ohira T, Arita M, Ebrahimi N, et al. (2006) RvE1 protects from local inflammation and osteoclast- mediated bone destruction in periodontitis. FASEB J 20: 401–403.
[9]
Offenbacher S (1996) Periodontal diseases: pathogenesis. Ann Periodontol 1: 821–878.
[10]
Page RC, Kornman KS (1997) The pathogenesis of human periodontitis: an introduction. Periodontol 2000 14: 9–11.
[11]
Goodson JM, Tanner AC, Haffajee AD, Sornberger GC, Socransky SS (1982) Patterns of progression and regression of advanced destructive periodontal disease. Journal of Clinical Periodontology 9: 472–481.
[12]
Van Dyke TE, Warbington M, Gardner M, Offenbacher S (1990) Neutrophil surface protein markers as indicators of defective chemotaxis in LJP. J Periodontol 61: 180–184.
[13]
(2000) Parameter on aggressive periodontitis. American Academy of Periodontology. J Periodontol 71: 867–869.
[14]
Meng H, Xu L, Li Q, Han J, Zhao Y (2007) Determinants of host susceptibility in aggressive periodontitis. Periodontol 2000 43: 133–159.
[15]
Kantarci A, Oyaizu K, Van Dyke TE (2003) Neutrophil-mediated tissue injury in periodontal disease pathogenesis: findings from localized aggressive periodontitis. J Periodontol 74: 66–75.
[16]
Van Dyke TE, Zinney W, Winkel K, Taufiq A, Offenbacher S, et al. (1986) Neutrophil function in localized juvenile periodontitis. Phagocytosis, superoxide production and specific granule release. J Periodontol 57: 703–708.
[17]
Shapira L, Gordon B, Warbington M, Van Dyke TE (1994) Priming effect of Porphyromonas gingivalis lipopolysaccharide on superoxide production by neutrophils from healthy and rapidly progressive periodontitis subjects. J Periodontol 65: 129–133.
[18]
Shapira L, Warbington M, Van Dyke TE (1994) TNF alpha and IL-1 beta in serum of LJP patients with normal and defective neutrophil chemotaxis. J Periodontal Res 29: 371–373.
[19]
Serhan CN (2007) Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol 25: 101–137.
[20]
Serhan CN, Hamberg M, Samuelsson B (1984) Lipoxins: novel series of biologically active compounds formed from arachidonic acid in human leukocytes. Proc Natl Acad Sci U S A 81: 5335–5339.
[21]
Serhan CN (2005) Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution. Prostaglandins Leukot Essent Fatty Acids 73: 141–162.
[22]
Schwab JM, Chiang N, Arita M, Serhan CN (2007) Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447: 869–874.
[23]
Merched AJ, Ko K, Gotlinger KH, Serhan CN, Chan L (2008) Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB Journal 22: 3595–3606.
[24]
Tabas I (2010) Macrophage death and defective inflammation resolution in atherosclerosis. Nature Reviews Immunology 10: 36–46.
[25]
Mattoscio D, Evangelista V, De Cristofaro R, Recchiuti A, Pandolfi A, et al. (2010) Cystic fibrosis transmembrane conductance regulator (CFTR) expression in human platelets: impact on mediators and mechanisms of the inflammatory response. FASEB Journal 24: 3970–3980.
[26]
Majno G, Joris I (2004) Cells, tissues, and disease : principles of general pathology. New York: Oxford University Press. xxviii, 1005 p.
[27]
Gronert K, Kantarci A, Levy BD, Clish CB, Odparlik S, et al. (2004) A molecular defect in intracellular lipid signaling in human neutrophils in localized aggressive periodontal tissue damage. J Immunol 172: 1856–1861.
[28]
Furman MI, Barnard MR, Krueger LA, Fox ML, Shilale EA, et al. (2001) Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction. J Am Coll Cardiol 38: 1002–1006.
[29]
Nicu EA, Van der Velden U, Nieuwland R, Everts V, Loos BG (2009) Elevated platelet and leukocyte response to oral bacteria in periodontitis. J Thromb Haemost 7: 162–170.
[30]
Heasman PA, Collins JG, Offenbacher S (1993) Changes in crevicular fluid levels of interleukin-1 beta, leukotriene B4, prostaglandin E2, thromboxane B2 and tumour necrosis factor alpha in experimental gingivitis in humans. Journal of Periodontal Research 28: 241–247.
[31]
Pouliot M, Clish CB, Petasis NA, Van Dyke TE, Serhan CN (2000) Lipoxin A(4) analogues inhibit leukocyte recruitment to Porphyromonas gingivalis: a role for cyclooxygenase-2 and lipoxins in periodontal disease. Biochemistry 39: 4761–4768.
[32]
Dennison DK, Van Dyke TE (1997) The acute inflammatory response and the role of phagocytic cells in periodontal health and disease. Periodontology 2000 14: 54–78.
[33]
Oh SF, Pillai PS, Recchiuti A, Yang R, Serhan CN (2011) Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation. Journal of Clinical Investigation 121: 569–581.
[34]
Kantarci A, Hasturk H, Van Dyke TE (2006) Host-mediated resolution of inflammation in periodontal diseases. Periodontol 2000 40: 144–163.
[35]
Medzhitov R, Janeway C Jr (2000) Innate immunity. N Engl J Med 343: 338–344.
[36]
Dave S, Batista EL Jr, Van Dyke TE (2004) Cardiovascular disease and periodontal diseases: commonality and causation. Compend Contin Educ Dent 25: 26–37.
[37]
Friedewald VE, Kornman KS, Beck JD, Genco R, Goldfine A, et al. (2009) The American Journal of Cardiology and Journal of Periodontology Editors' Consensus: periodontitis and atherosclerotic cardiovascular disease. American Journal of Cardiology 104: 59–68.
[38]
Spanbroek R, Grabner R, Lotzer K, Hildner M, Urbach A, et al. (2003) Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis. Proc Natl Acad Sci U S A 100: 1238–1243.
[39]
Dwyer JH, Allayee H, Dwyer KM, Fan J, Wu H, et al. (2004) Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. N Engl J Med 350: 29–37.
[40]
Serhan CN, Jain A, Marleau S, Clish C, Kantarci A, et al. (2003) Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-lipoxygenase and endogenous anti-inflammatory lipid mediators. J Immunol 171: 6856–6865.
[41]
Serhan CN, Sheppard KA (1990) Lipoxin formation during human neutrophil-platelet interactions. Evidence for the transformation of leukotriene A4 by platelet 12-lipoxygenase in vitro. J Clin Invest 85: 772–780.
[42]
Yamamoto K, Kobayashi T, Grossi S, Ho AW, Genco RJ, et al. (2004) Association of Fcgamma receptor IIa genotype with chronic periodontitis in Caucasians. Journal of Periodontology 75: 517–522.
[43]
Hasturk H, Kantarci A, Goguet-Surmenian E, Blackwood A, Andry C, et al. (2007) Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J Immunol 179: 7021–7029.
[44]
Haworth O, Cernadas M, Yang R, Serhan CN, Levy BD (2008) Resolvin E1 regulates interleukin 23, interferon-gamma and lipoxin A4 to promote the resolution of allergic airway inflammation. Nat Immunol 9: 873–879.
[45]
Seki H, Fukunaga K, Arita M, Arai H, Nakanishi H, et al. (2010) The anti-inflammatory and proresolving mediator resolvin E1 protects mice from bacterial pneumonia and acute lung injury. J Immunol 184: 836–843.
[46]
Ohira T, Arita M, Omori K, Recchiuti A, Van Dyke TE, et al. (2009) Resolvin E1 receptor activation signals phosphorylation and phagocytosis. Journal of Biological Chemistry.
[47]
Requirand P, Gibert P, Tramini P, Cristol JP, Descomps B (2000) Serum fatty acid imbalance in bone loss: example with periodontal disease. Clin Nutr 19: 271–276.
[48]
Dewhirst FE, Moss DE, Offenbacher S, Goodson JM (1983) Levels of prostaglandin E2, thromboxane, and prostacyclin in periodontal tissues. J Periodontal Res 18: 156–163.
[49]
Offenbacher S, Odle BM, Gray RC, Van Dyke TE (1984) Crevicular fluid prostaglandin E levels as a measure of the periodontal disease status of adult and juvenile periodontitis patients. J Periodontal Res 19: 1–13.
[50]
El-Sharkawy H, Aboelsaad N, Eliwa M, Darweesh M, Alshahat M, et al. (2010) Adjunctive treatment of chronic periodontitis with daily dietary supplementation with omega-3 Fatty acids and low-dose aspirin. J Periodontol 81: 1635–1643.
[51]
Hart TC, Marazita ML, McCanna KM, Schenkein HA, Diehl SR (1993) Reevaluation of the chromosome 4q candidate region for early onset periodontitis. Human Genetics 91: 416–422.
[52]
Kinane DF, Hart TC (2003) Genes and gene polymorphisms associated with periodontal disease. Critical Reviews in Oral Biology and Medicine 14: 430–449.
[53]
Zhang Y, Syed R, Uygar C, Pallos D, Gorry MC, et al. (2003) Evaluation of human leukocyte N-formylpeptide receptor (FPR1) SNPs in aggressive periodontitis patients. Genes Immun 4: 22–29.
[54]
Maney P, Emecen P, Mills JS, Walters JD (2009) Neutrophil formylpeptide receptor single nucleotide polymorphism 348T>C in aggressive periodontitis. Journal of Periodontology 80: 492–498.
[55]
Dona M, Fredman G, Schwab JM, Chiang N, Arita M, et al. (2008) Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Blood 112: 848–855.
[56]
Yang R CN, Oh SF, Serhan CN (2011) Metabolomics-lipidomics of eicosanoids and docosanoids generated by phagocytes. Curr Protoc Immunol.
[57]
Krishnamoorthy S, Recchiuti A, Chiang N, Yacoubian S, Lee CH, et al. (2010) Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proceedings of the National Academy of Sciences of the United States of America.
