Abstract
To investigate effect of MMLA, an inhibitor of nitric oxide (NO) production, on regulation of inflammatory responses to Bordetella pertussis infection, mice were infected intranasally, and treated with various concentrations of MMLA. Ten days after infection, mice treated with MMLA at dosage of 100 mg/kg, given intraperitoneally in a single dose or for 5 consecutive days, showed at histopathologic examination, a significant decrease of intensity of inflammation (scores, 0.6 +/- 0.2 and 0.9 +/- 0.5 respectively). A decrease of cellular accumulation of neutrophils and lymphocytes in the bronchoalveolar lavage (BAL) fluid was observed in infected mice treated with MMLA, especially at dosage of 10 mg/kg, given in a single dose intraperitoneally. In addition, BP-infected mice treated with MMLA (100 mg/kg, intraperitoneally) for 5 consecutive days showed higher mortality rate than untreated mice infected with B. pertussis, and the number of B. pertussis in lungs of mice treated with MMLA was significantly increased. However, MMLA treatment of infected mice had some effect on levels of IFN-gamma and nitrite/nitrate (end-stable products of NO) in the BAL fluid. This study indicates that NO may play a role either as microbiocidal agent or as a modulator of immune regulation, inasmuch as it may upregulate tissue inflammatory response to B. pertussis.
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- Adams L. B., Hibbs J. B., Jr, Taintor R. R., Krahenbuhl J. L. Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. J Immunol. 1990 Apr 1;144(7):2725–2729. [PubMed] [Google Scholar]
- Beckman J. S., Beckman T. W., Chen J., Marshall P. A., Freeman B. A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620–1624. doi: 10.1073/pnas.87.4.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chan J., Xing Y., Magliozzo R. S., Bloom B. R. Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. J Exp Med. 1992 Apr 1;175(4):1111–1122. doi: 10.1084/jem.175.4.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Denis M. Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates. Cell Immunol. 1991 Jan;132(1):150–157. doi: 10.1016/0008-8749(91)90014-3. [DOI] [PubMed] [Google Scholar]
- Ding A. H., Nathan C. F., Stuehr D. J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [PubMed] [Google Scholar]
- Flesch I. E., Kaufmann S. H. Mechanisms involved in mycobacterial growth inhibition by gamma interferon-activated bone marrow macrophages: role of reactive nitrogen intermediates. Infect Immun. 1991 Sep;59(9):3213–3218. doi: 10.1128/iai.59.9.3213-3218.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Granger D. L., Hibbs J. B., Jr, Perfect J. R., Durack D. T. Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages. J Clin Invest. 1988 Apr;81(4):1129–1136. doi: 10.1172/JCI113427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Green S. J., Nacy C. A., Meltzer M. S. Cytokine-induced synthesis of nitrogen oxides in macrophages: a protective host response to Leishmania and other intracellular pathogens. J Leukoc Biol. 1991 Jul;50(1):93–103. doi: 10.1002/jlb.50.1.93. [DOI] [PubMed] [Google Scholar]
- James S. L., Glaven J. Macrophage cytotoxicity against schistosomula of Schistosoma mansoni involves arginine-dependent production of reactive nitrogen intermediates. J Immunol. 1989 Dec 15;143(12):4208–4212. [PubMed] [Google Scholar]
- Jorens P. G., Van Overveld F. J., Bult H., Vermeire P. A., Herman A. G. L-arginine-dependent production of nitrogen oxides by rat pulmonary macrophages. Eur J Pharmacol. 1991 Aug 6;200(2-3):205–209. doi: 10.1016/0014-2999(91)90573-9. [DOI] [PubMed] [Google Scholar]
- Kubes P., Suzuki M., Granger D. N. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651–4655. doi: 10.1073/pnas.88.11.4651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuo H. P., Liu S., Barnes P. J. The effect of endogenous nitric oxide on neurogenic plasma exudation in guinea-pig airways. Eur J Pharmacol. 1992 Oct 20;221(2-3):385–388. doi: 10.1016/0014-2999(92)90728-m. [DOI] [PubMed] [Google Scholar]
- Liew F. Y., Millott S., Parkinson C., Palmer R. M., Moncada S. Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine. J Immunol. 1990 Jun 15;144(12):4794–4797. [PubMed] [Google Scholar]
- Marletta M. A. Nitric oxide synthase: aspects concerning structure and catalysis. Cell. 1994 Sep 23;78(6):927–930. doi: 10.1016/0092-8674(94)90268-2. [DOI] [PubMed] [Google Scholar]
- Roach T. I., Kiderlen A. F., Blackwell J. M. Role of inorganic nitrogen oxides and tumor necrosis factor alpha in killing Leishmania donovani amastigotes in gamma interferon-lipopolysaccharide-activated macrophages from Lshs and Lshr congenic mouse strains. Infect Immun. 1991 Nov;59(11):3935–3944. doi: 10.1128/iai.59.11.3935-3944.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saukkonen K., Cabellos C., Burroughs M., Prasad S., Tuomanen E. Integrin-mediated localization of Bordetella pertussis within macrophages: role in pulmonary colonization. J Exp Med. 1991 May 1;173(5):1143–1149. doi: 10.1084/jem.173.5.1143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shellito J. E., Kolls J. K., Olariu R., Beck J. M. Nitric oxide and host defense against Pneumocystis carinii infection in a mouse model. J Infect Dis. 1996 Feb;173(2):432–439. doi: 10.1093/infdis/173.2.432. [DOI] [PubMed] [Google Scholar]
- Torre D., Ferrario G., Bonetta G., Perversi L., Speranza F. In vitro and in vivo induction of nitric oxide by murine macrophages stimulated with Bordetella pertussis. FEMS Immunol Med Microbiol. 1996 Feb;13(2):95–99. doi: 10.1016/0928-8244(95)00089-5. [DOI] [PubMed] [Google Scholar]
- Torre D., Ferrario G., Bonetta G., Perversi L., Tambini R., Speranza F. Effects of recombinant human gamma interferon on intracellular survival of Bordetella pertussis in human phagocytic cells. FEMS Immunol Med Microbiol. 1994 Sep;9(3):183–188. doi: 10.1111/j.1574-695X.1994.tb00492.x. [DOI] [PubMed] [Google Scholar]
- Torre D., Pugliese A., Speranza F., Fiori G. P., Perversi L., Marone P., Tambini R. Interferon-gamma levels in serum and bronchoalveolar lavage fluid of mice infected with Bordetella pertussis. J Infect Dis. 1993 Mar;167(3):762–765. doi: 10.1093/infdis/167.3.762. [DOI] [PubMed] [Google Scholar]
- Torre D., Quadrelli C., Pugliese A., Maggiolo F. Effect of betamethasone in lungs of mice treated with lymphocytosis-promoting factor of Bordetella pertussis. J Infect Dis. 1986 Aug;154(2):238–244. doi: 10.1093/infdis/154.2.238. [DOI] [PubMed] [Google Scholar]
- Torre D., Tambini R., Ferrario G., Bonetta G. Treatment with steroids in children with pertussis. Pediatr Infect Dis J. 1993 May;12(5):419–420. doi: 10.1097/00006454-199305000-00021. [DOI] [PubMed] [Google Scholar]
