The complement system has been implicated as both a pathogenic mechanism and a means of protection in periodontal diseases. It is well known that bacteria activate complement; such activation can initiate a number of events, including bacterial opsonization and killing, release of inflammatory agents, and modulation of other immune reactions. Cleavage of complement proteins has been observed in gingival fluids from individuals with periodontal disease and some investigators have observed complement deposition in diseased gingival tissues. Furthermore, a number of bacteria from individuals with periodontal diseases have been found to activate complement in vitro; some of these organisms appear to have the capacity to evade opsonization due to their proteolytic capacity. However, concrete evidence is not yet available that indicates that complement activation occurs in human periodontal disease and is important in either its pathogenesis or in protection against bacterial virulence factors.
References
1.
Dalmasso, A.P., Complement in the pathophysiology and diagnosis of human diseases, Crit. Rev. Clin. Lab. Sci., 24, 123, 1986.
2.
Cooper, N.R., The classical complement pathway: activation and regulation of the first complement component, Adv. Immunol., 37, 151, 1985.
3.
Müller-Eberhard, H.J. and Schreiber, R.D., Molecular biology and chemistry of the alternative pathway of human complement, Adv. Immunol., 29, 1, 1980.
4.
Müller-Eberhard, H.J., The membrane attack complex of complement, Ann. Rev. Immunol., 4, 503, 1986.
5.
Sim, R.B., Malhotra, V., Day, A.J., and Erdei, A., Structure and specificity of complement receptors, Immunol. Lett., 14, 183, 1987.
6.
Mollnes, T.E. and Lachman, P.J., Regulation of complement, Scand. J. lmmunol., 27, 127, 1988.
7.
Frank, M.M., Complement in the pathophysiology of human disease, N. Engl. J. Med., 316, 1525, 1987.
8.
Wright, S.D. and Griffin, F.M., Jr., Activation of phagocytic cells' C3 receptors for phagocytosis, J. Leuk. Biol., 38, 327, 1985.
9.
Joiner, K.A., Complement evasion by bacteria and parasites, Ann. Rev. Microbiol., 42, 201, 1988.
10.
Allison, A.C., Schorlemmer, H.U., and Bitter-Suermann, D., Activation of complement by the alternative pathway as a factor in the pathogenesis of periodontal disease, Lancet, 1001, 1976.
11.
Genco, R.J., Mashimo, P.A., and Ellison, S.A., Antibody-mediated effects on the periodontium, J. Periodontol., 45, 330, 1974.
12.
Genco, R.J., Immunoglobulins and periodontal disease, J. Periodontol., 41, 8, 1970.
13.
Mergenhagen, S.E., Tempel, T.R., and Snyderman, R., Immunologic reactions and periodontal inflammation, J. Dent. Res., 49, 256, 1970.
14.
Mergenhagen, S.E., Complement as a mediator of inflammation: formation of biologically active products after interaction of serum complement with endotoxins and antigen-antibody complexes, J. Periodontol., 41, 202, 1970.
15.
Mergenhagen, S.E., Complement as a mediator of the inflammatory response: interaction of complement with mammalian and bacterial enzymes, J. Dent. Res., 51,251, 1972.
16.
Snyderman, R., Role for endotoxin and complement in periodontal tissue destruction, J. Dent. Res., 51(Suppl.), 356, 1972.
17.
Platt, D., Crosby, R.G., and Dalbow, M.H., Evidence for the presence of immunoglobulins and antibodies in inflamed periodontal tissues, J. Periodontol., 41, 215, 1970.
18.
Shillitoe, E.J. and Lehner, T., Immunoglobulins and complement in crevicular fluid, Arch. Oral Biol., 17, 241, 1972.
19.
Attstrom, R., Laurell, A.B., Lahsson, V., and Sjoholm, A., Complement factors in gingival crevice material from healthy and inflamed gingiva in humans, J. Periodontal Res., 10, 19, 1975.
20.
Schenkein, H.A. and Genco, R.J., Gingival fluid and serum in periodontal diseases. I. Quantitative study of immunoglobulins, complement components, and other plasma proteins, J. Periodontol., 48, 772, 1977.
21.
Schenkein, H.A. and Genco, R.J., Gingival fluid and serum in periodontal diseases. II. Evidence for cleavage of complement components C3, C3 proactivator (factor B) and C4 in gingival fluid, J. Periodontol., 48, 778, 1977.
22.
Tollefsen, T. and Saltvedt, E., Comparative analysis of gingival fluid and plasma by crossed immunoelectrophoresis, J. Periodontal Res., 15, 96, 1980.
23.
Niekrash, C.E. and Patters, M.R., Simultaneous assessment of complement components C3, C4, and B and their cleavage products in human gingival fluid. II. Longitudinal changes during periodontal therapy, J. Periodontal Res., 20, 268, 1985.
24.
Patters, M.R., Schenkein, H.A., and Weinstein, A., A method for detection of complement cleavage in gingival fluid, J. Dent. Res., 58, 1620, 1979.
25.
Niekrash, C.E., Patters, M.R., and Lang, N.P., The relationship of complement cleavage in gingival fluid to periodontal diseases, J. Periodontal Res., 19, 622, 1984.
26.
Niekrash, C.E. and Patters, M.R., Simultaneous assessment of complement components C3, C4, and B and their cleavage products in human gingival fluid. 1. Reliability of the method, J. Periodontal Res., 20, 260, 1985.
27.
Patters, M.R., Niekrash, C.E., and Lang, N.P., Assessment of complement cleavage in gingival fluid during experimental gingivitis in man, J. Clin. Periodontol., 16, 33, 1989.
28.
Schenkein, H.A., Cianciola, L., and Genco, R.J., Complement activation in gingival pocket fluid from patients with periodontosis and severe periodontitis, J. Dent. Res., 55 (Special Issue B: Abstr. #581), 1976.
29.
Courts, F.J., Boakle, R.J., Fudenberg, H.H., and Silverman, M.S., Detection of functional complement components in gingival crevicular fluid from humans with periodontal disease, J. Periodontal Res., 56, 327, 1977.
30.
Niekrash, C.E. and Patters, M.R., Assessment of complement cleavage in gingival fluid in humans with and without periodontal disease, J. Periodontal Res., 21, 233, 1986.
31.
Ranney, R.R., Ruddy, S., Tew, J.G., Welshimer, H.J., Palcanis, K.G., and Segreti, A., Immunological studies of young adults with severe periodontitis. I. Medical evaluation and humoral factors, J. Periodontal Res., 16, 390, 1981.
32.
Johnson, R.J., Matthews, J.L., Stone, M.J., Hurt, W.C., and Newman, J.T., Immunopathology of periodontal disease, J. Periodontol., 51, 705, 1980.
33.
Norman, M.E., Baehni, P.C., Tsai, C.-C., Stoller, N., McArthur, W.P., and Taichman, N.S., Studies of host responses during experimental gingivitis in humans. II. Changes in acute phase reactants, serum immunoglobulins, and complement during the development of gingival inflammation, J. Periodontal Res., 14, 361, 1979.
34.
Henry, C.A., Ungchusri, T., Charbeneau, T.D., and Winford, T.E., Relationships of serum opsonins and complement in human experimental gingivitis, J. Periodontol., 58, 177, 1987.
Toto, P.D., Lin, L., and Gargiulo, A., Identification of C3a, IgG, and IgM in inflamed human gingiva, J. Dent. Res., 57, 696, 1978.
37.
Toto, P.D., Lin, L.-M., and Gauguilo, A.W., Immunoglobulins and complement in human periodontitis, J. Periodontol., 49, 631, 1978.
38.
Clagett, J.A. and Page, R.C., Insoluble immune complexes and chronic periodontal diseases in man and the dog, Arch. Oral Biol., 23, 153, 1978.
39.
Nikolopoulou-Papaconstantinou, A.-A., Johannessen, A.C., and Kristoffersen, T., Deposits of immunoglobulins, complement, and immune complexes in inflamed human gingiva, Acta Odontol. Scand., 45, 187, 1987.
40.
Pekovic, D.D. and Fillery, E.D., Identification of bacteria in immunopathological mechanisms of human periodontal diseases, J. Periodontal Res., 19, 329, 1984.
41.
Okada, H. and Silverman, M.S., Chemotactic activity in periodontal disease. I. The role of complement in monocyte chemotaxis, J. Periodontal Res., 14, 20, 1979.
42.
Okada, H. and Silverman, M.S., Chemotactic activity in periodontal disease. II. The generation of complement-derived chemotactic factors, J. Periodontal Res., 14, 147, 1979.
43.
Schonfeld, S.E., Drury, G.J., and Herles, S.M., Complement fixing activity in diseased human gingival tissues, J. Periodontal Res., 16, 574, 1981.
44.
Lally, E.T., McArthur, W.P., and Baehni, P.C., Biosynthesis of complement components in chronically inflamed gingiva, J. Periodontal Res., 17, 257, 1982.
45.
Lally, E.T., Baehni, P.C., and McArthur, W.P., Local immunoglobulin synthesis in periodontal disease, J. Periodontal Res., 15, 159, 1980.
46.
Ranney, R.R. and Zander, H.A., Allergic periodontal disease in sensitized squirrel monkeys, J. Periodontol., 41, 12, 1970.
47.
Nisengard, R.J., Beutner, E.H., Neugeboren, N.J., Neiders, M., and Asaro, J., Experimental induction of periodontal disease with Arthus-type reactions, Clin. Immunol. Immunopathol., 8, 97, 1977.
48.
Attstrom, R. and Larsson, U., Effect of decomplementation by carragheenan on the migration of neutrophils and monocytes into dog gingival crevices, J. Periodontal Res., 9, 165, 1974.
49.
Kahnberg, K.E., Lindhe, J., and Attstrom, R., The role of complement in initial gingivitis. I. The effect of decomplementation by cobra venom factor, J. Periodontal Res., 11, 269, 1976.
50.
Kahnberg, K.E., Lindhe, J., and Attstrom, R., The effect of decomplementation by caragheenan on experimental initial gingivitis in hyperimmune dogs, J. Periodontal Res., 12, 479, 1977.
51.
Wennstrom, J.L., Heijl, L., Lindhe, J., and Socransky, S., Migration of gingival leukocytes mediated by plaque bacteria, J. Periodontal Res., 15, 363, 1980.
52.
Anderson, D.C., Schmalsteig, F.C., Kohl, S., Arnaout, M.A., Tosi, M.F., Dana, M., Buffone, G.J., Hughes, B.J., Brinkley, B.R., Dickey, W.D., Abramson, J.S., Springer, T., Boxer, L.A., Hollers, J.M., and Smith, C.W., Abnormalities of polymorphonuclear leukocyte function associated with a heritable deficiency of high molecular weight surface glycoproteins (GP138): common relationship to diminished cell adherence, J. Clin. Invest., 74, 536, 1984.
53.
Anderson, D.C., Schmalstieg, F.C., Finegold, M.J., Hughes, B.J., Rothlein, R., Miller, L.J., Kohl, S., Tosi, M.F., Jacobs, R.L., Waldrop, T.C., Goldman, A.S., Shearer, W.T., and Springer, T., The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features, J. Infect. Dis., 152, 668, 1985.
54.
Waldrop, T.C., Anderson, D.C., Hallmon, W.W., Schmalstieg, F.C., and Jacobs, R.L., Periodontal manifestations of the heritable Mac-1, LFA-1, deficiency syndrome, J. Periodontol., 58, 400, 1987.
55.
Rizzo, A., Absorption of bacterial exodotoxin into rabbit gingival pocket tissues, Periodontics, 6, 65, 1968.
56.
Nisengard, R. and Jarrett, C., Coating of subgingival bacteria with immunoglobulins and complement, J. Periodontol., 47, 518, 1976.
57.
Hawley, C.E. and Falkler, W.A., Antigens of Leptotrichia buccalis. II. Their reaction with complement-fixing IgM in human sera, J. Periodontal Res., 10, 216, 1975.
58.
Hawley, C.E. and Falkler, W.A., Anticomplementary activity of Fusobacterium polymorphum in normal and C4-deficient sources of guinea pig complement, Infect. Immun., 18, 124, 1977.
59.
Hawley, C.E. and Falkler, W.A., The anticomplementary activity of lipopolysaccharide preparations and sonicates from a strain of Fusobacteria nucleatum, J. Periodontal Res., 13, 24, 1978.
60.
Tsai, C.C., Nilsson, U.R., McArthur, W.P., and Taichman, N.S., Activation of the complement system by some gram-positive oral bacteria, Arch. Oral Biol., 22, 309, 1977.
61.
Nygren, H., Dahlen, G., and Nilsson, L., Human complement activation by lipopolysaccharides from Bacteroides oris, Fusobacterium nucleatum, and Veilonella parvula, Infect. Immun., 26, 391, 1979.
62.
Okuda, K. and Takazoe, I., Activation of complement by dental plaque, J. Periodontal Res., 15, 232, 1980.
63.
Bolton, R.W. and Dyer, J.K., Human complement activation by purified Capnocytophaga exopolysaccharide. Measurement by radioimmunoassay, J. Periodontal Res., 21, 634, 1986.
64.
Okuda, K., Yanagi, K., and Takazoe, I., Complement activation by Propionibacterium acnes and Bacteroides melaninogenicus, Arch. Oral Biol., 23, 911, 1978.
65.
Sundqvist, G., Bengston, A., and Carlsson, J., Generation and degradation of the complement fragment C5a in human serum by Bacteroides gingivalis, Oral Microbiol Immunol., 3, 103, 1988.
66.
Olsson-Wennstrom, A., Wennstrom, J.L., Mergenhagen, S.E., and Siraganian, R.P., The mechanism of basophil histamine release in patients with periodontal disease, Clin. Exp. Immunol., 33, 166, 1978.
67.
Abiko, Y., Hayakawa, M., Murai and al, E., Glycylprolyl dipeptidylaminopeptidase from Bacteroides gingivalis, J. Dent. Res., 64, 106, 1985.
68.
Barua, P.K., Neiders, M.E., Topolnycky, A., Zambon, J.J., and Birkedal-Hansen, H., Purification of an 80,000-Mr glycylprolyl peptidase from Bacteroides gingivalis, Infect. Immun., 57, 2522, 1989.
69.
Fujimura, S. and Nakamura, T., Isolation and characterization of a protease from Bacteroides gingivalis, Infect. Immun., 55, 716, 1987.
70.
Grenier, D. and McBride, B.C., Isolation of a membrane-associated Bacteroides gingivalis glycylprolyl protease, Infect. Immun., 55, 3131, 1987.
71.
Sorsa, T., Uitto, V.-J., Suomalainen, K., Turto, H., and Lindy, S., A trypsin-like protease from Bacteroides gingivalis: partial purification and characterization, J. Periodontal Res., 22, 375, 1987.
72.
Tsutsui, H., Kinouchi, T., Wakano, Y., and Ohnishi, Y., Purification and characterization of a protease from Bacteroides gingivalis 381, Infect. Immun., 55, 420, 1987.
73.
Yoshimura, F., Nishikata, M., Suzuki, T., and Ai, E., Characterization of a trypsin-like protease from the bacterium Bacteroides gingivalis isolated from human dental plaque, Arch. Oral Biol., 29, 559, 1984.
74.
Killan, M., Degradation of immunoglobulins A 1, A2, and G by suspected principal periodontal pathogens, Infect. Immun., 34, 757, 1981.
75.
Carlsson, J., Herrmann, B.F., Höfling, J.F., and Al, E., Degradation of human proteinase inhibitors alpha-1 antitrypsin and alpha-2- macroglobulin by Bacteroides gingivalis, Infect. Immun., 43, 644, 1984.
76.
Nillson, T., Carlsson, J., and Sundqvist, G., Inactivation of key factors of the plasma proteinase cascade systems by Bacteroides gingivalis, Infect. Immun., 50,467, 1985.
77.
Sundqvist, G.K., Carlsson, J., Herrmann, B.F., Hofling, J., and Vaatainen, A., Degradation in vivo of the C3 protein of guinea-pig complement by a pathogenic strain of Bacteroides gingivalis, Scand. J. Dent. Res., 92, 14, 1984.
78.
Sundqvist, G., Carlsson, J., Herrmann, B., and Tarnvik, A., Degradation of human immunoglobulins G and M and complement factors C3 and C5 by black pigmented Bacteroides, J. Med. Microbiol., 19, 85, 1985.
79.
Schenkein, H.A., The effect of periodontal proteolytic Bacteroides sp. on proteins of the human complement system, J. Periodontal Res., 23, 187, 1988.
80.
Schenkein, H.A., Failure of Bacteroides gingivalis W83 to accumulate bound C3 following opsonization with serum, J. Periodontal Res., 24, 20, 1989.
81.
Schenkein, H.A. and Berry, C.R., Production of chemotactic factors for neutrophils following the interaction of Bacteroides gingivalis with purified C5, J. Periodontal Res., 23, 308, 1988.
82.
Sundqvist, G. and Johansson, E., Bactericidal effect of pooled human serum on Bacteroides melaninogenicus, Bacteroides asaccharolyticus, and Actinobacillus actinomycetemcomitans, Scand. J. Dent. Res., 90, 29, 1982.
83.
Okuda, K., Kato, T., Naito, Y., Ono, M., Kikuchi, Y., and Takazoe, I., Susceptibility of Bacteroides gingivalis to bactericidal activity of human serum, J. Dent. Res., 65, 1024, 1986.
84.
Baker, P. and Wilson, M., Opsonic IgG antibody against Actinobacillus actinomycetemcomitans in localized juvenile periodontitis, Oral. Microbiol. Immunol., 4, 98, 1989.
85.
Wilson, M.E., Burstein, R., Jonak-Urbanczyk, J.T., and Genco, R.J., Sensitivity of Capnocytophaga sp. to bactericidal properties of human serum, Infect. Immun., 50, 123, 1985.
86.
Boehringer, H., Berthold, P.H., and Taichman, N.S., Studies on the interaction of human neutrophils with plaque spirochetes, J. Periodontal Res., 21, 195, 1986.
87.
Mallison, S.M., III, Szakal, A.K., Ranney, R.R., and Tew, J.G., Antibody synthesis specific for non-oral antigens in inflamed gingiva, Infect. Immun., 56, 823, 1988.
88.
Kupp, L.I., Tew, J.G., Schenkein, H.A., and Kosco, M.H., Migration of germinal center B cells in response to chemoattractant(s), J. Dent. Res., 68, 171, 1989.
