Effect of exogenous nitric oxide on murine immune response induced by Aggregatibacter actinomycetemcomitans lipopolysaccharide.
OBJECTIVE
Elevated nitric oxide (NO) has been associated with destructive periodontal disease. The aim of the present study was to test the hypothesis that exogenous NO may inhibit a protective immune response to Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) in a murine model.


METHODS
Mice of the BALB/c strain were sham immunized, immunized with A. actinomycetemcomitans LPS, treated with S-nitroso-N-acetyl penicillamine (SNAP; a NO donor) and immunized with A. actinomycetemcomitans LPS or treated with SNAP plus 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and immunized with A. actinomycetemcomitans LPS. All animals were then challenged subcutaneously with viable A. actinomycetemcomitans. The serum-specific immunoglobulin G (IgG) subclasses and both interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) as well as splenic inducible nitric oxide synthase (iNOS) activity before and after bacterial challenge were assessed. The diameter of skin lesions was determined. Groups of mice were treated with l-N(6)-(1-iminoethyl)-lysine (l-NIL), an iNOS inhibitor, or 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), a guanylyl cyclase inhibitor, prior to injections with SNAP and/or A. actinomycetemcomitans LPS, and the skin lesions were assessed.


RESULTS
Treatment with SNAP increased the iNOS activity, suppressed both serum-specific IgG2a and IFN-gamma levels, and delayed the healing of the lesions. These SNAP-induced immune alterations were restored by treatment with carboxy-PTIO. Pretreatment with l-NIL resulted in partial healing, whereas pretreatment with ODQ induced a delayed healing of the lesions.


CONCLUSIONS
The present study suggests that exogenous NO may suppress a protective T helper 1-like murine immune response to A. actinomycetemcomitans LPS by an endogenous NO-independent but a cyclic GMP-dependent mechanism.
Sosroseno
W
W
School of Dentistry, AIMST University, Semeling, Bedong, Kedah, Darul Aman, Malaysia. wsosroseno@yahoo.com
Bird
P S
PS
Seymour
G J
GJ
D000189:Actinobacillus Infections / Q000276:immunology; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D001565:Benzoates / Q000494:pharmacology; D006152:Cyclic GMP / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007093:Imidazoles / Q000494:pharmacology; D007111:Immunity, Cellular / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology*; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D017192:Skin Diseases, Bacterial / Q000276:immunology; D013154:Spleen / Q000201:enzymology; D018417:Th1 Cells / Q000276:immunology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000907:Antibodies, Bacterial; D001565:Benzoates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; C090663:N(6)-(1-iminoethyl)lysine; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011810:Quinoxalines; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D015847:Interleukin-4; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D007371:Interferon-gamma; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D008239:Lysine