Oxidative and nonoxidative killing of Actinobacillus actinomycetemcomitans by human neutrophils

Actinobacillus actinomycetemcomitans is a facultative gram-negative microorganism which has been implicated as an etiologic agent in localized juvenile periodontitis and in subacute bacterial endocarditis and abscesses. Although resistant to serum bactericidal action and to oxidant injury mediated by superoxide anion (O2-) and hydrogen peroxide (H2O2), this organism is sensitive to killing by the myeloperoxidase-hydrogen peroxide-chloride system (K.T. Miyasaki, M.E. Wilson, and R.J. Genco, Infect. Immun. 53:161-165, 1986). In this study, we examined the sensitivity of A. actinomycetemcomitans to killing by intact neutrophils under aerobic conditions, under anaerobic conditions, and under aerobic conditions in the presence of the heme-protein inhibitor sodium cyanide. Intact neutrophils killed opsonized A. actinomycetemcomitans under aerobic and anaerobic conditions, and the kinetics of these reactions indicated that both oxidative and nonoxidative mechanisms were operative. Oxidative mechanisms contributed significantly, and most of the killing attributable to oxidative mechanisms was inhibited by sodium cyanide, which suggested that the myeloperoxidase-hydrogen peroxide-chloride system participated in the oxidative process. We conclude that human neutrophils are capable of killing A. actinomycetemcomitans by both oxygen-dependent and oxygen-independent pathways, and that most oxygen-dependent killing requires myeloperoxidase activity.

[1]  M. Wilson,et al.  Killing of Actinobacillus actinomycetemcomitans by the human neutrophil myeloperoxidase-hydrogen peroxide-chloride system , 1986, Infection and immunity.

[2]  M. Cohen,et al.  Phagocytic cells in periodontal defense. Periodontal status of patients with chronic granulomatous disease of childhood. , 1985, Journal of periodontology.

[3]  T. Ganz,et al.  DEFENSINS: NATURAL PEPTIDE ANTIBIOTICS IN HUMAN NEUTROPHILS , 1986 .

[4]  S. Mergenhagen,et al.  Gingivitis and oral ulceration in patients with neutrophil dysfunction. , 1985, Journal of oral pathology.

[5]  A. Tärnvik,et al.  Anaerobic phagocytosis, killing, and degradation of Streptococcus pneumoniae by human peripheral blood leukocytes , 1985, Infection and immunity.

[6]  M. Wilson,et al.  Resistance of Actinobacillus actinomycetemcomitans and differential susceptibility of oral Haemophilus species to the bactericidal effects of hydrogen peroxide , 1984, Infection and immunity.

[7]  D. Malamud,et al.  Extraction and isolation of a leukotoxin from Actinobacillus actinomycetemcomitans with polymyxin B , 1984, Infection and immunity.

[8]  S. Weiss,et al.  Long-lived oxidants generated by human neutrophils: characterization and bioactivity. , 1983, Science.

[9]  W. J. Loesche,et al.  Relationship between oxygen tension and subgingival bacterial flora in untreated human periodontal pockets , 1983, Infection and immunity.

[10]  J. Slots,et al.  Suppression of the periodontopathic microflora in localized juvenile periodontitis by systemic tetracycline. , 1983, Journal of clinical periodontology.

[11]  R. Genco,et al.  Serology of oral Actinobacillus actinomycetemcomitans and serotype distribution in human periodontal disease , 1983, Infection and immunity.

[12]  C. Deluca,et al.  Studies of leukotoxin from Actinobacillus actinomycetemcomitans using the promyelocytic HL-60 cell line , 1983, Infection and immunity.

[13]  K. Lewin,et al.  Identification of tissue-invading bacteria in human periodontal disease. , 1982, Journal of periodontal research.

[14]  J. Spitznagel,et al.  Outer membrane mutants of Salmonella typhimurium LT2 have lipopolysaccharide-dependent resistance to the bactericidal activity of anaerobic human neutrophils , 1982, Infection and immunity.

[15]  S. Holt,et al.  Collagenolytic activity associated with Bacteroides species and Actinobacillus actinomycetemcomitans. , 1982, Journal of periodontal research.

[16]  E. Johansson,et al.  Bactericidal effect of pooled human serum on Bacteroides melaninogenicus, Bacteroides asaccharolyticus and Actinobacillus actinomycetemcomitans. , 1982, Scandinavian journal of dental research.

[17]  W. Mcarthur,et al.  Immune suppression induced by Actinobacillus actinomycetemcomitans. I. Effects on human peripheral blood lymphocyte responses to mitogens and antigens. , 1982, Journal of immunology.

[18]  R. Genco,et al.  Leukotoxic effects of Actinobacillus actinomycetemcomitans. Modulation by serum components. , 1981, Journal of periodontal research.

[19]  P. Kiley,et al.  Characterization of the lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4 and N27 , 1980, Infection and immunity.

[20]  E. Pick,et al.  A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture. , 1980, Journal of immunological methods.

[21]  R. Genco,et al.  Actinobacillus actinomycetemcomitans in human periodontal disease: a cross-sectional microbiological investigation. , 1980, Infection and immunity.

[22]  P. Ward,et al.  Impaired neutrophil chemotaxis in patients with juvenile and rapidly progressing periodontitis. , 1979, Journal of periodontal research.

[23]  T. Stelmaszyńska,et al.  N-(2-Oxoacyl)amino acids and nitriles as final products of dipeptide chlorination mediated by the myeloperoxidase/H2O2/Cl- system. , 1978, European journal of biochemistry.

[24]  H. Odeberg,et al.  Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes. , 1978, The Journal of biological chemistry.

[25]  R. Selvaraj,et al.  Enhanced killing of myeloperoxidase-coated bacteria in the myeloperoxidase-H2O2-Cl- system. , 1978, The Journal of infectious diseases.

[26]  R. Page,et al.  Defective neutrophil chemotaxis in juvenile periodontitis , 1977, Infection and immunity.

[27]  J. Metcalf,et al.  H2O2 release from human granulocytes during phagocytosis. Relationship to superoxide anion formation and cellular catabolism of H2O2: studies with normal and cytochalasin B-treated cells. , 1977, The Journal of clinical investigation.

[28]  J. Mcghee,et al.  A bactericidal effect for human lactoferrin. , 1977, Science.

[29]  C. J. Oss,et al.  Defective polymorphonuclear leukocyte function in a human periodontal disease , 1977, Nature.

[30]  I. Olsson,et al.  Microbicidal mechanisms of human granulocytes: synergistic effects of granulocyte elastase and myeloperoxidase or chymotrypsin-like cationic protein , 1976, Infection and immunity.

[31]  J. Slots.  The predominant cultivable organisms in juvenile periodontitis. , 1976, Scandinavian journal of dental research.

[32]  H. Odeberg,et al.  Antibacterial activity of cationic proteins from human granulocytes. , 1975, The Journal of clinical investigation.

[33]  D. Roos,et al.  Quantitative aspects of the production of superoxide radicals by phagocytizing human granulocytes. , 1975, The Journal of laboratory and clinical medicine.

[34]  G. Mandell.  Bactericidal Activity of Aerobic and Anaerobic Polymorphonuclear Neutrophils , 1974, Infection and immunity.

[35]  R. Selvaraj,et al.  Oxidative Peptide Cleavage and Decarboxylation by the MPO-H2O2-Cl− Antimicrobial System , 1974, Infection and immunity.

[36]  S. Klebanoff,et al.  Role of myeloperoxidase-mediated antimicrobial systems in intact leukocytes. , 1972, Journal of the Reticuloendothelial Society.

[37]  S. Klebanoff.  Myeloperoxidase: Contribution to the Microbicidal Activity of Intact Leukocytes , 1970, Science.

[38]  M. Wilson,et al.  Influence of endogenous catalase activity on the sensitivity of the oral bacterium Actinobacillus actinomycetemcomitans and the oral haemophili to the bactericidal properties of hydrogen peroxide. , 1985, Archives of oral biology.

[39]  J. Zambon.  Actinobacillus actinomycetemcomitans in human periodontal disease. , 1985, Journal of clinical periodontology.

[40]  W. Mcarthur,et al.  Leukotoxic activity in different strains of the bacterium Actinobacillus actinomycetemcomitans isolated from juvenile periodontitis in man. , 1981, Archives of oral biology.

[41]  B. Babior,et al.  The killing of pathogens by phagocytes. , 1981, Annual review of medicine.

[42]  R. Allen.  Free-Radical Production by Reticuloendothelial Cells , 1980 .