Alteration of the cytokine phenotype in an experimental lung granuloma model by inhibiting nitric oxide
| Autor: | C M, Hogaboam, S W, Chensue, M L, Steinhauser, G B, Huffnagle, N W, Lukacs, R M, Strieter, S L, Kunkel |
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| Rok vydání: | 1998 |
| Předmět: |
Lung Diseases
Granuloma Respiratory Tract Neutrophils Tumor Necrosis Factor-alpha Nitric Oxide Synthase Type II Th1 Cells Nitric Oxide Tuberculin Interleukin-12 Interleukin-10 Eosinophils Interferon-gamma Mice NG-Nitroarginine Methyl Ester Mice Inbred CBA Animals Cytokines Female Interleukin-4 Nitric Oxide Synthase Lung |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 159(11) |
| ISSN: | 0022-1767 |
| Popis: | Pulmonary granulomatous inflammation modulated by IFN-gamma and IL-12 is also associated with augmented inducible nitric oxide synthase (NOS II). To address the role of increased nitric oxide synthesis in this model, mice received daily i.p. injections of NG-nitro-L-arginine-methyl ester (L-NAME; 8 mg/kg) during both the 2-wk immunization period with purified protein-derivative (PPD) and the subsequent lung challenge with PPD-coated Sepharose beads. Other groups of animals received saline, L-NAME or NG-nitro-D-arginine-methyl ester (D-NAME; 8 mg/kg) during the pulmonary embolization period and not the PPD sensitization period. On day 4 post-PPD bead challenge, PCR analysis of the whole lung revealed that NOS II expression appeared to be similar in both of the L-NAME treatment protocols. L-NAME-treated mice in both dosing protocols had lung lesions that were significantly larger than granuloma lesions measured in mice that received saline or D-NAME. The enlarged lesions from L-NAME-treated mice contained markedly greater numbers of neutrophils and eosinophils. Equivalent numbers of PPD-activated dispersed cells from whole lungs of L-NAME-treated mice produced significantly higher levels of IL-4 and IL-10 and smaller amounts of IL-12 and IFN-gamma compared with similar lung cultures derived from control or D-NAME-treated mice. Levels of C-C chemokines such as monocyte chemoattractant protein-1 (MCP-1), C10, and macrophage inflammatory protein-1alpha (MIP-1alpha) were also significantly elevated in lung cultures from L-NAME-treated mice compared with controls. Thus, nitric oxide regulates the size and cellular composition of the Th1-type lung granuloma, possibly through its effects on the cytokine and chemokine profile associated with this lesion. |
| Databáze: | OpenAIRE |
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