Table 2 Human conditions associated with mononuclear phagocyte NOS2 expression a
Disorder | Reference | Cell | Assay | Comments |
|---|---|---|---|---|
Liver disease | ||||
Alcoholic hepatitis | Hunt and Goldin, 1992 (32) | Mo | Nitrite production in vitro | None by those from normal individuals; no treatment |
Alcoholic cirrhosis | Criado-Jimenez et al., 1995 (106) | MNC | Nitrite | Blocked by L-Arg analogue |
Alcoholic cirrhosis with ascites | Laffi et al., 1995 (107) | Mo | L-Arg to L-Cit, inhibition of platelet aggregation | Inhibited by L-Arg analogues |
Cirrhosis | Masini et al., 1995(108) | Mo | L-Arg to L-Cit, inhibition of platelet aggregation | Higher in Mo from patients with cirrhosis; inhibited by NMMA |
Hepatitis C patients | Sharara et al., 1997 (76) | Mo, MNC | Nitrite, nitrate, immunoblot, L-Arg to L-Cit, RT-PCR | Induction of NOS2 activity and Ag content by in vivo treatment of hepatitis C patients; correlation of anti-viral activity of IFN-α with degree of NOS2 induction |
Chronic viral hepatitis | Majano et al., 1998 (109) | MNC | Immunohistology, in situ hybridization | In chronic active hepatitis B or C patients, NOS2 protein and mRNA noted in hepatocytes, with only mRNA noted in MNC in hepatitis |
Lung disease | ||||
Lung inflammation | Kobzik et al., 1993 (111) | Alv Mac | NOS2 immunohistology | |
Acute lung injury (ARDS) | Haddad et al., 1994 (113) | Alv Mac | Nitrotyrosine immunohistology | Presumed NO formation leading to nitrotyrosine |
Lung inflammation (bronchiectasis and bronchopneumonia) | Tracey et al., 1994 (112) | Alv Mac | NOS2 immunohistology | No staining in cells from normal lung |
Acute lung injury (ARDS, sepsis, pneumonia) | Kooy et al., 1995 (114) | Alv Mac | Nitrotyrosine immunohistology | Presumed NO formation leading to nitrotyrosine |
Pulmonary tuberculosis | Kumar et al., 1995(117) | Mo | Nitrite | Higher in cells from patients tuberculosis pretreatment; enhanced in vitro by LPS, PPD, PMA, latex spheres |
Pulmonary tuberculosis | Nicholson et al., 1996 (118) | Alv Mac | Immunohistology, immunoblot, RT-PCR | Increased NOS2 in cells from patients with tuberculosis |
Pulmonary tuberculosis | Tunctan et al., 1998 (119) | Mo | Nitrite; smooth muscle relaxation | Increased nitrite production by LPS-treated cells from normal subjects but not those from tuberculosis patients; supernatant media from LPS-treated cells of tuberculosis patients had increased smooth muscle relaxing activity |
Pulmonary tuberculosis | Wang et al., 1998 (120) | Alv Mac | Flow cytometry, immunohistology, nitrite | Higher NOS2 expression and nitrite production by cells from tuberculosis patients; nitrite production correlated significantly with exhaled NO concentration |
Obliterative bronchiolitis in lung transplant patients | McDermott et al., 1997 (115) | Alv Mac | Immunohistology for NOS2 and nitrotyrosine | Co-localization of NOS2 and peroxynitrite with Mac |
Pulmonary fibrosis | Nozaki et al., 1997 (116) | Alv Mac | Immunocytology and immunoblot for NOS2 and nitrotyrosine, RT-PCR | Produced by alv Mac from patients with pulmonary fibrosis after in vitro challenge with BCG; NMMA inhibited Mac-mediated BCG killing |
Cardiovascular disease | ||||
Atherosclerosis | Beckman et al., 1994 (121) | Vessel Mac | Nitrotyrosine immunohistology | Presumed NO formation leading to nitrotyrosine |
Myocardial infarct | Wildhirt et al., 1995 (126) | Myocardial Mac | Immunohistology | NOS2 in infarcted myocardium co-localized with Mac |
Atherosclerosis | Buttery et al., 1996 (122) | Atherosclerotic plaque Mac | Immunohistology, immunoblot, in situ hybridization, nitrotyrosine | Nitrotyrosine associated with macrophages |
Giant cell arteritis | Weyand et al., 1996 (127) | Arterial Mac | Immunohistology | NOS2 in intimai Mac in giant cell arteritis |
Accelerated arteriosclerosis in transplanted hearts | Lafond-Walker et al., 1997 (125) | Coronary artery Mac | Immunohistology, in situ hybridization | NOS2 associated with Mac |
Atherosclerosis | Wilcox et al., 1997 (123) | Vessel Mac | In situ hybridization, immunohistology | No NOS2 in normal vessels; in atherosclerotic vessels, Mac expressed NOS2 and NOS1 |
Atherosclerosis | Luoma et al., 1998 (124) | Arterial Mac | Immunohistology | NOS2 and nitrotyrosine associated with Mac |
Allergic disease | ||||
Hay fever, asthma | Mautino et al., 1994 (79) | Mo | Nitrite | IL-4 treatment |
Arthritis | ||||
RA and inflammatory osteoarthritis | Sakurai et al, 1995 (128) | Synovial Mac | Nitrite, immunohistology, immunoblot, RT-PCR | Inhibited by L-Arg analogue |
RA and osteoarthritis | Mclnnes et al., 1996 (129) | Synovial Mac | Nitrite, RT-PCR, immunohistology | NOS2 in synovial Mac and synovial fibroblasts |
RA | St. Clair et al., 1996 (67) | Mo, MNC | Nitrite, nitrate, immunoblot, L-Arg to L-Cit | Increased L-Arg to L-Cit activity and NOS2 Ag in freshly isolated cells from patients with RA; increased responsiveness of MNC of RA patients to IFN-γ in vitro; inhibited by NMMA |
RA | Grabowski et al., 1997 (130) | Synovial Mac | Immunohistology | NOS2 associated chiefly with CD68+ Mac by immunohistology; more NOS2 in RA vs. osteoarthritis; no NOS2 noted in tissues from normal subjects (hip fractures) |
RA | Perkins et al., 1998 (131) | Mo, MNC | Immunoblot, RT-PCR, L-Arg to L-Cit | Increased L-Arg to L-Cit activity, NOS2 Ag, NOS2 mRNA in MNC from patients with RA; anti-TNF antibody treatment in vivo reduced the increased NOS activity and NOS2 Ag expression |
Inflammatory response to foreign body (joint prostheses) | Moilanen et aL, 1997 (132) | Foreign body Mac | Immunohistology, RT-PCR | NOS2 associated with Mac |
Loosened bone prosethesis | Watkins et al., 1997 (133) | Mac around loosened bone hip prostheses | In situ hybridization, immunohistology | No NOS2 in synovial cells |
Cancer | ||||
Breast cancer | Thomsen et al., 1994 (136) | Breast cancer Mac | Anti-NOS2 Ab immunocytology, nitrite and nitrate, L-Arg to L-Cit | NOS2 associated with CD68 + Mac by immunohistol |
Various metastatic cancers to pleural or peritoneal spaces | Wang et al., 1996 (68) | Pleural or peritoneal Mac | Nitrite | More NO production by Mac from patients with cancer |
Colon cancer | Ambs et aL, 1998 (135) | Colon cancer MNC | L-Arg to L-Cit, immunohistology for NOS2 and nitrotyrosine, immunoblot, RT-PCR | NOS2 in tumors (more in adenomas than in carcinomas), but low in normal tissue; present in MNC, tumor cells, and endothelial cells; nitrotyrosine in MNC |
Parasitic disease | ||||
African children: normal and malarious | Anstey et al., 1996 (138) | MNC | Immunoblot | MNC NOS2 expression in normal Tanzanian children; increased NOS2 in asymptomatic and mild malaria; markedly decreased NOS2 in cerebral malaria |
Renal disease | ||||
IgA nephropathy & proliferative glomerulonephritis | Kashem et al., 1996 (66) | Kidney Mac, Mo | Immunohistology, RT-PCR | NOS2 associated with Mac |
IgA nephropathy, lupus nephritis, membranous nephropathy, and minimal change neprhotic syncrome | Furusu et al., 1998 (139) | Kidney Mac | Immunohistology, in situ hybridization | NOS2 primarily in mesangial cells and glomerular epithelial cells; inverse levels of expression of NOS3 and NOS2 in the kidneys with NOS2 correlating with degree of glomerular injury |
Bowel disease | ||||
Crohn’s disease, ulcerative colitis, diverticulitis | Singer et al., 1996 (140) | Bowel Mac | Immunohistology, RT-PCR | Found associated with Mac only at sites of inflammation |
Ulcerative colitis | Ikeda et al., 1997 (141) | Bowel Mac | Immunohistology | Increased NOS2 in areas of inflammation |
Celiac disease | ter Steege et al., 1997 (143) | Bowel Mac | Immunohistology | Increased NOS2 and nitrotyrosine in Mac in disease sites |
Multiple sclerosis | ||||
Multiple sclerosis | Bo et al., 1994 (144) | Brain Mac | RT-PCR | NOS2 NADPH diaphorase activity detectable in brains of MS patients |
Multiple sclerosis | Bagasra et al., 1995 (145) | Brain Mac | Immunohistology, RT-in situ-PCR | NOS2 mRNA and nitrotyrosine in Mac of patients with multiple sclerosis and absent in “control” brains |
Multiple sclerosis | De Groot et al., 1997 (146) | Brain Mac | Immunohistology; nitrite | In brains of patients with multiple sclerosis, Mac positive for both NOS2 and “cNOS;” isolated Mac produced NO |
Multiple sclerosis | Hooper et al, 1997 (147) | Brain Mac | Immunohistology, RT-in situ-PCR | NOS2 in brain Mac from multiple sclerosis patients |
Pregnancy | ||||
Pregnancy | Myatt et al., 1997 (148) | Placental Mac (Hofbauer cells) | Immunohistology, RT-PCR | NOS2 associated with Mac |
Pregnancy | Eis et al., 1997 (150) | Fetal membrane Mac | Immunohistology | NOS2 associated with membrane Mac; greater NOS2 expression in preterm labor vs. term labor |
Pregnancy | Zarlingo et al., 1997 (149) | Placental Mac | Immunohistology, immunoblot | |
Miscellaneous conditions | ||||
Trauma | Kim et al., 1995 (153) | Mo | Nitrite, nitrate | Higher NO production in PBMC from trauma patients; some reduction of NO production by IL-13 |
Grave’s disease (thyrotoxicosis) | Lopez-Moratalla et al., 1996 (152) | Mo | Immunocytology | NOS2 in freshly isolated Mo from Grave’s; increased activity induced by in vitro treatment with peptides from thyroid autoantigens |
Sickle cell disease | Dias-Da-Motta et al., 1996 (154) | PBMC | Inhibition of platelet aggregation | Inhibited by L-Arg analogue-production noted only in presence of SOD; more activity in cells from patients with sickle cell disease |