PMID- 9548500 OWN - NLM STAT- MEDLINE DCOM- 19980420 LR - 20131121 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 159 IP - 11 DP - 1997 Dec 1 TI - Alteration of the cytokine phenotype in an experimental lung granuloma model by inhibiting nitric oxide. PG - 5585-93 AB - 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. FAU - Hogaboam, C M AU - Hogaboam CM AD - Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA. FAU - Chensue, S W AU - Chensue SW FAU - Steinhauser, M L AU - Steinhauser ML FAU - Huffnagle, G B AU - Huffnagle GB FAU - Lukacs, N W AU - Lukacs NW FAU - Strieter, R M AU - Strieter RM FAU - Kunkel, S L AU - Kunkel SL LA - eng GR - 1P50HL56402/HL/NHLBI NIH HHS/United States GR - HL31963/HL/NHLBI NIH HHS/United States GR - HL35276/HL/NHLBI NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Cytokines) RN - 0 (Tuberculin) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) RN - 207137-56-2 (Interleukin-4) RN - 31C4KY9ESH (Nitric Oxide) RN - 82115-62-6 (Interferon-gamma) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) SB - IM MH - Animals MH - Cytokines/*metabolism MH - Eosinophils/immunology MH - Female MH - Granuloma, Respiratory Tract/*immunology MH - Interferon-gamma/metabolism MH - Interleukin-10/metabolism MH - Interleukin-12/metabolism MH - Interleukin-4/metabolism MH - Lung/enzymology MH - Lung Diseases/*immunology MH - Mice MH - Mice, Inbred CBA MH - NG-Nitroarginine Methyl Ester/pharmacology MH - Neutrophils/immunology MH - Nitric Oxide/antagonists & inhibitors/biosynthesis/*physiology MH - Nitric Oxide Synthase/metabolism MH - Nitric Oxide Synthase Type II MH - *Th1 Cells MH - Tuberculin/pharmacology MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 1998/04/21 00:00 MHDA- 1998/04/21 00:01 CRDT- 1998/04/21 00:00 PHST- 1998/04/21 00:00 [pubmed] PHST- 1998/04/21 00:01 [medline] PHST- 1998/04/21 00:00 [entrez] PST - ppublish SO - J Immunol. 1997 Dec 1;159(11):5585-93.