Table 1 NO production and NOS2 expression analysis in human mononuclear phagocytes a
Reference | Cell type | In vitro Rx | Assay | Detected | Comments |
|---|---|---|---|---|---|
1989 | |||||
Salvemini et al. (31) | MNC | None | Inhibit platelet aggregation | Yes | |
1990 | |||||
Cameron et al. (40) | Alv Mac, Perit Mac | IFN-γ | Nitrite, nitrate, L-Arg to L-Cit | No | No evidence of NO involvement in anti-cryptococcal effects |
1991 | |||||
Denis (41) | Mo | Mycobacterium avium, TNF, GM-CSF | Nitrite | Yes | |
Sherman et al. (42) | Alv Mac | LPS, IFN-γ | Nitrite, L-Cit | Yes | No increase in nitrite, but increased L-Cit with IFN-γ treatment |
1992 | |||||
Harwix et al. (44) | Mo | LPS, IFN-γ | Nitrite | No | No evidence of NO generation in tumoricidal Mo |
Hunt and Goldin (32) | Mo | None | Nitrite | Yes | More in Mo from patients with alcoholic hepatitis |
Muñoz-Fernández et al. (43) | Mo | IFN-γ, TNF | Nitrite | Yes | Anti-Trypanosomal cruzi activity inhibited by NMMA |
Murray and Teitelbaum (45) | Mo | IFN-γ | Nitrite | No | No inhibition of anti-microbial effect by NMMA; also no NO production by Mo from patients receiving IFN-γ in vivo |
Padgett and Pruett (46) | Mo | LPS, IFN-γ, opsonized zymosan, SEB, PMA | Nitrite | No | |
1993 | |||||
Belenky et al. (96) | Mo | fMLP | Chemotaxis inhibition by NMMA | Yes | L-Arg analogues inhibited Chemotaxis to fMLP |
Ben-Efraim et al. (47) | Perit Mac | LPS, PMA, IND | Nitrite | No | |
Bermudez (48) | Mo | TNF, GM-CSF, IFN-γ, Listeria monocytogenes, M. avium | Nitrite | No | No inhibition of anti-microbial effect by NMMA or arginase |
Condino-Neto et al. (151) | MNC | None | Inhibit platelet aggregation | Yes | Inhibition blocked by an L-Arg analogue |
Keller et al. (49) | BM-derived Mac | IL-3, M-CSF, GM-CSF | Nitrite | No | Tumoricidal effect not inhibited by NMMA |
Kobzik et al. (111) | Alv Mac | None | Histology with diaphorase and anti-NOS2 Ab | Yes | More expression in those from patient with inflammation |
Martin and Edwards (34) | Mo | Culture | Nitrite | Yes | Tumoricidal effect inhibited by NMMA |
Middleton et al. (33) | MNC | None | Smooth muscle relaxation | Yes | Relaxation inhibited by NMMA, Hb, or methylene blue |
Naotunne et al. (92) | MNC | Malaria extracts | Inhibition of antimalarial action by NMMA | Yes | Inhibition of MNC anti-malarial effects by NMMA |
Petit et al. (36) | Mo | None | Nitrite | No | No inhibition of anti-tumor activity by L-Arg analogues |
Sakai and Milstien (50) | MNC | LPS, IFN-γ | Nitrite | No | No effect of adding BH4 or sepiapterin |
Schneemann et al. (51) | Mo | LPS, IFN-γ, GM-CSF, TNF, IL-2, PPD, Listeria, Moraxella | Nitrite, L-Arg consumption, L-Cit production, NOS activity | No | No benefit from adding BH4 |
Wickramasinghe and Hasan (35) | BM Mac | None | Nitrite | Yes | Inhibited by NMMA |
1994 | |||||
Barnewall and Rikihisa (52) | Mo, THP-1 | IFN-γ, Ehrlichia chaffeensis, PMA | Nitrite | No | Monocyte-mediated anti-Ehrlichia effects not dependent on NO production |
Beckman et al. (121) | Arterial atheromata Mac | None | Immunohistology for nitrotyrosine | Yes | Nitrotyrosine as evidence of peroxynitrite (and NO) formation in situ |
Bo et al. (144) | Brain Mac | None | RT-PCR | Yes | NOS2 mRNA noted in brain tissue from patients with multiple sclerosis |
De Maria et al. (97) | Mo | Anti-CD69 Ab, LPS, IFN-γ | Nitrite and nitrate, tumor cytotoxicity | Yes | Inhibited by NMMA; LPS and IFN-γ without effect |
Dumarey et al. (91) | MNC | Live M. avium, LPS, IFN-γ, TNF | Nitrite and nitrate | Yes | Inhibited by NMMA; only a certain strain effective |
Essery et al. (52) | MNC | LPS, SEB | Nitrite | Yes | |
Gyan et al. (54) | MNC | IFN-γ | Nitrite | Yes | Nitrite production and anti-malarial activity inhibited by NMMA |
Haddad et al. (113) | Alv Mac | None | Immunocytology, immunohistology | Yes | Nitrotyrosine as evidence of peroxynitrite (and NO) formation in situ in patients with acute lung injury |
Kolb et al. (79) | Mo | IL-4, IFN-γ | Nitrite | Yes | Sequential IL-4 then IFN-γ treatment increased nitrite; inhibited by NMMA |
Leibovich et al. (55) | Mo | LPS | Nitrite and nitrate | Yes | Inhibited by L-Arg analogues |
Martin and Edwards (56) | Mo | IFN-γ | Nitrite | Yes | Increase with time in culture; no augmentation by IFN-γ |
Mautino et al. (80) | Mo | IL-4 | Nitrite | Yes | Heterogenous production; allergic subjects higher; inhibited by NMMA |
Paul-Eugene et al. (81) | MNC | IL-4 | Nitrite | Yes | NMMA inhibited IL-4-induced IgE production |
Pietraforte et al. (94) | Mo | gp120 | Nitrite and spin trapping (DMPO) | Yes | Inhibited by L-Arg analogues |
Reiling et al. (60) | Mo, U937, THP-1, Mono-Mac6 | LPS, IFN-γ | RT-PCR | Yes | NOS3 mRNA in “resting” Mo and leukemia cells, and NOS2 mRNA in treated Mo |
Thomsen et al. (136) | Gynecological cancer MNC | None | L-Arg to L-Cit, immunohistology, immunoblot | No | NOS2 in tumor cells, but not in leukocytes |
Tracey et al. (112) | Alv Mac | None | Immunohistology | Yes | NOS2 antigen in Mac from patients with bronchiectasis and pneumonia |
Tufano et al. (95) | Mo | Yersinia enterocolitica porins | Nitrite | Yes | Some LPS contamination in porin |
Zembala et al. (57) | Mo | Selected tumor cells, IL-2, LPS, TNF, IFN-γ | Nitrite | Yes | Inhibited by L-Arg analogues; no effect of IL-2, LPS, TNF, IFN-γ |
1995 | |||||
Bagasra et al. (145) | Brain Mac | None | Northern blot; RT-in situ-PCR, immunohistology | Yes | NOS2 mRNA and nitrotyrosine in Mac of patients with multiple sclerosis and absent in “control” brains |
Bose and Farnia (59) | MNC | IFN-γ, TNF, IL-1 | Nitrite | Yes | |
Bukrinsky et al. (61) | Mo | M-CSF, HIV-1 infection, IFN-γ, LPS; co-culture with astroglial cells | Nitrite, RT-PCR, EPR (Fe-DETC) | Yes | All cells cultured with M-CSF, and then infected/treated with other additives; inhibited by NMMA |
Chu et al. (37) | Alv Mac | IFN-γ, IL-1, TNF, IL-6 | RT-PCR | Yes | Structural diversity in the 5′ untranslated region of mRNA |
Criado-Jimenez et al. (106) | MNC | None | Nitrite | Yes | Higher activity cells from cirrhosis patients; L-Arg analogue inhibited |
Laffi et al. (107) | Mo | None | L-Arg to L-Cit, inhibition of platelet aggregation | Yes | Higher activity in cells from patients with cirrhosis; inhibited by L-Arg analogues |
Kim et al. (153) | Mo | LPS | Nitrite, nitrate | Yes | Higher NO production in PBMC from trauma patients; some reduction of NO production by IL-13 |
Kooy et al. (114) | Alv Mac | None | Immunohistology for nitrotyrosine | Yes | Nitrotyrosine as evidence of peroxynitrite (and NO) formation in situ in patients with acute lung injury |
Kumar et al. (117) | Mo | LPS, PPD, PMA, latex spheres | Nitrite, L-Cit | Yes | Higher in cells from patients with tuberculosis pretreatment |
Lecoanet-Henchoz et al. (82) | Mo | sCD23, anti-CD11b, anti-CD11c | Nitrite, nitrate | Yes | Inhibited by L-Arg analogue |
Masini et al. (108) | Mo | None | L-Arg to L-Cit, inhibition of platelet aggregation | Yes | Higher in Mo from patients with cirrhosis; inhibited by NMMA |
Paul-Eugene et al. (84) | PBMC | IL-4 | Inhibition of IL-4-induced increase in IL-4 and sCD23 production | Yes | Phenomenon blocked by NMMA |
Paul-Eugene et al. (83) | Mo | IL-4, IgE-immune complexes | Nitrite | Yes | Inhibited by NMMA |
Paul-Eugene et al. (85) | Mo | IL-4, sCD23, IFN-γ | Nitrite; L-Cit | Yes | Inhibited by L-Arg analogue or anti-CD23 |
Perez-Mediavilla et al. (98) | MNC | ECM peptides | Nitrite; immunocytology | Yes | Inhibited by NMMA |
Sakurai et al. (128) | Synovial Mac | None | Nitrite, immunohistology, immunoblot, RT-PCR | Yes | RA and inflammatory osteoarthritis patients; inhibited by L-Arg analogue |
Siedlar et al. (58) | Mo | DeTa tumor cells | Nitrite | Yes | DeTa tumor-induced nitrite formation blocked by antibodies against MHC class I or II, CD44, LFA-3 (CD58), VLA-β1 (CD29) |
Thomsen et al. (134) | Breast cancer Mac | None | Anti-NOS2 Ab immunocytology, nitrite and nitrate, L-Arg to L-Cit | Yes | NOS2 associated with CD68+ Mac by immunohistology |
Vouldoukis et al. (87) | Mo | Anti-CD23 Ab, IgE-IC, IL-4, IFN-γ | Nitrite, immunoblot, RT-PCR, L-Arg to L-Cit | Yes | Inhibited by NMMA |
Weinberg et al. (30) | Mo, Perit Mac | LPS, IFN-γ, TNF, IL-1, IL-2, IL-4, GM-CSF, IL-7, IL-6, VD3, PMA, ConA, PHA, A23187, bacteria, mycobacteria, HIV-1 | Nitrite, nitrate, immunocytology, immunoblot, RT-PCR, Northern blot, RNAse protection, L-Arg to L-Cit | Yes | Generally low levels (Mac > Mo) compared to mouse Mac; no effect of adding BH4; mRNA detected only by RT-PCR |
Wildhirt et al. (126) | Myocardial Mac | None | Immunohistology | Yes | NOS2 in infarcted myocardium colocalized with Mac |
Zinetti et al. (64) | MNC, THP-1 | LPS | Nitrite; NMMA- or Hb-or Mbinhibitable LPS-induced TNF secretion and inhibition of THP-1 proliferation | Yes | No nitrite production noted, but indirect evidence of NO production |
1996 | |||||
Anstey et al. (138) | MNC | None | Immunoblot, serum and urine nitrite/nitrate | Yes | MNC NOS2 expression in normal Tanzanian children; increased NOS2 in asymptomatic and mild malaria; markedly decreased NOS2 in cerebral malaria |
Buttery et al. (122) | Atherosclerotic plaque Mac | None | Immunohistology, immunoblot, in situ hybridization, nitrotyrosine | Yes | Nitrotyrosine as evidence of peroxynitrite (and NO) formation in situ |
Condino-Neto et al. (65) | MNC | IFN-γ in vivo, LPS in vitro | Nitrite, nitrate, inhibition of platelet aggregation | No | |
Dias-Da-Motta et al. (154) | PBMC | PMA, zymosan | Inhibition of platelet aggregation | Yes | Inhibited by L-Arg analogue-production noted only in presence of SOD; more activity in cells from patients with sickle cell disease |
Dugas et al. (86) | Mo | Anti-CD23 antibody | NMMA-induced inhibition of anti-CD23 antibody induced IL-10 production | Yes | |
Eissa et al. (38) | Alv Mac | None | RT-PCR | Yes | Alternative splicing of mRNA |
Kashem et al. (66) | Kidney Mac, Mo | IFN-γ, TNF | Immunohistology, RT-PCR | Yes | Assoc with CD68+ Mac in kidneys with IgA nephropathy and proliferative glomerulonephritis; NOS2 mRNA expression in normal Mo treated in vitro with IFN-γ + TNF |
Liu et al. (63) | Fetal microglial cells | IL-1, TNF, IFN-γ, LPS, TGF-β, IL-10, HIV-1, gp160 | Nitrite, immunocytology, Northern blot, immunoblot | No | |
Lopez-Moratalla et al. (152) | Mo | Peptides from thyroid autoantigens | Immunocytology | Yes | NOS2 in freshly isolated Mo from Grave’s; increased activity induced by in vitro treatment with peptides from thyroid autoantigens |
Magazine et al. (100) | Mo | Morphine | NO-specific amperometric probe | Yes | Inhibited by L-Arg analogues or naloxone |
McInnes et al. (129) | Synovial Mac | SEB | Nitrite, RT-PCR, immunohistology | Yes | NOS2 in synovial Mac and synovial fibroblasts |
McLachlan et al. (99) | Mo | Dehydroepi-androsterone, LPS | Nitrite | Yes | |
Nicholson et al. (118) | Alv Mac | None | Immunohistology, immunoblot, RT-PCR | Yes | Increased in cells from patients with tuberculosis |
Singer et al. (140) | Colonic Mac | None | Immunohistology for NOS2 and nitrotyrosine, RT-PCR | Yes | Found only in inflammatory mucosal areas in patients with ulcerative colitis, Crohn’s disease, and diverticulitis |
St. Clair et al. (67) | Mo, MNC | LPS, IFN-γ | Nitrite, nitrate, immunoblot, L-Arg to L-Cit | Yes | 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 |
Stefano et al. (102) | Mo | Anandamide (tetrahydrocannabinol derivative) | NO-specific amperometric probe | Yes | Inhibited by L-Arg analogues and a cannabinoid antagonist |
Wang et al. (68) | Mo; pleural and peritioneal Mac | LPS | Nitrite | Yes | More NO production if adherent to plastic; more NO production from tissue Mac from patients with cancer |
Weyand et al. (127) | Arterial Mac | None | Immunohistology | Yes | NOS2 in intimai Mac in giant cell arteritis |
1997 | |||||
Amin et al. (69) | Mo, HL-60 cells, U937 cells | TNF, IL-1, LPS | L-Arg to L-Cit, immunoblot, RT-PCR, Northern blot | Yes | NOS2 mRNA noted, but negative by immunoblot and L-Arg to L-Cit assay |
Aubry et al. (88) | Mo | sCD23, anti-CD11b, anti-CD11c | L-Arg to L-Cit, immunoblot, RT-PCR | Yes | Inhibited by NMMA; stimulated expression of NOS3 (NOS2 not studied) |
Bagasra et al. (62) | Brain Mac | None | RT-in situ-PCR, immunohistology | No | Absence of NOS2 mRNA and nitrotyrosine in brains of patients with AIDS |
Degroot et al. (146) | Brain Mac | None | Immunohistology; nitrite | Yes | In brains of patients with multiple sclerosis, Mac positive for both NOS2 and “cNOS;” isolated Mac produced NO |
Eis et al. (150) | Fetal membrane | None | Immunohistology | Yes | NOS2 in CD 14+fetal membrane Mac |
Grabowski et al. (130) | Synovial Mac | None | Immunohistology | Yes | NOS2 associated chiefly with CD68+Mac by immunohistol; more NOS2 in RA vs. osteoarthritis; no NOS2 noted in tissues from normal subjects (hip fractures) |
Hooper et al. (147) | Brain Mac | None | Immunohistology, RT-in situ-PCR | Yes | NOS2 in brain Mac from multiple sclerosis patients |
Ikeda et al. (141) | Bowel Mac | None | Immunohistology | Yes | Increased NOS2 expression in ulcerative colitis |
King et al. (103) | Mo, U937, THP-1 | Endothelin-1 | NO-specific amperometric probe | Yes | Effect blocked by ETB antagonist |
Lafond-Walker et al. (125) | Coronary artery Mac | None | Immunohistology, in situ hybridization | Yes | Only in accelerated graft arteriosclerosis in transplanted hearts; associated with CD68+Mac |
Lammas et al. (104) | Mo | ATP, BCG | Inhibition of Mo or BCG killing by L-Arg analogues | No | No inhibition of Mo or BCG killing by L-Arg analogues |
McDermott et al. (115) | Alv Mac | None | Immunohistology for NOS2 and nitrotyrosine | Yes | Lung transplant patients with obliterative bronchiolitis |
Moilanen et al. (132) | Foreign body Mac (joint prostheses) | None | L-Arg to L-Cit, immunohistology, RT-PCR | Yes | NOS2 associated with CD68+Mac |
Myatt et al. (148) | Placental Mac (Hofbauer cells) | None | Immunohistology, RT-PCR | Yes | NOS2 associated with CD 14+Mac |
Nozaki et al. (116) | Alv Mac | BCG | Immunocytology and immunoblot for NOS2 and nitrotyrosine, RT-PCR | Yes | Produced by alv Mac from patients with pulmonary fibrosis after in vitro challenge with BCG; NMMA inhibited Mac-mediated BCG killing |
Polack et al. (70) | Mo | LPS | NMMA inhibition of LPS-induced increased tissue factor | Yes | |
Saha et al. (71) | PBMC | Monophosphoryl lipid A | Nitrite, immunocytology; flow cytometry | Yes | Monophosphoryl lipid A stimulated but LPS did not; inhibited by L-Arg analogue |
Schneemann et al. (90) | MNC | IL-4, IFN-γ | Nitrite, L-Arg and L-Cit levels | No | |
Seitzer et al. (93) | Mo-derived multinucleated giant cells | Nippostrongylus br brasiliensis | RT-PCR | Yes | NOS2 mRNA noted in 15–21% of single giant cells |
Sharara et al. (76) | Mo, MNC | IFN-α in vitro and in vivo | Nitrite, nitrate, immunoblot, L-Arg to L-Cit, RT-PCR | Yes | Induction of NOS2 activity, mRNA, and Ag content by in vitro treatment of normal Mo, or in vivo treatment of hepatitis C patients; correlation of anti-viral activity of IFN-α with degree of NOS2 induction |
Snell et al. (72) | Mo | Polyribonucleotides, IFN-γ, IFN-α, IL-4 | Nitrite | Yes | No effect of LPS, IFN-γ, IFN-α, and IL-4 alone, but potentiation of polyribonucleotide effect; inhibited by NMMA |
ter Steege et al. (143) | Bowel Mac | None | Immunohistology | Yes | Increased NOS2 and nitrotyrosine in CD14/CD68+ Mac celiac disease |
Vitek et al. (105) | Mo | Polyinosinic-polycytidylic acid and apolipoprotein E | Nitrite | Yes | Amyloid beta peptide inhibited the apolipoprotein-E-induced increase |
Vouldoukis et al. (89) | Mo | Anti-CD23 Ab | Nitrite | Yes | IL-10 and IL-4 inhibited killing of Leishmania |
Watkins et al. (133) | Mac around loosened bone hip prostheses | None | In situ hybridization, immunohistology | Yes | No NOS2 in synovial cells |
Wilcox et al. (123) | Vessel Mac | None | In situ hybridization, immunohistology | Yes | Mac in atherosclerotic lesions expressed both NOS2 and NOS1 |
Zarlingo et al. (149) | Placental Mac | None | Immunohistology, immunoblot | Yes | |
1998 | |||||
Ambs et al. (135) | Tumor Mac | None | L-Arg to L-Cit, immunohistology for NOS2 and nitrotyrosine, immunoblot, RT-PCR | Yes | 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 |
Aymerich et al. (101) | Mo | β-endorphin | Immunohistology | Yes | |
Furusu et al. (139) | Kidney Mac | None | Immunohistology, in situ hybridization | Yes | 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 |
Luoma et al. (124) | Arterial Mac | None | Immunohistology | Yes | NOS2 and nitrotyrosine associated with Mac |
Majano et al. (109) | Liver MNC | None | Immunohistology, in situ hybridization | Yes | In chronic active hepatitis B or C patients, NOS2 protein and mRNA noted in hepatocytes, with only mRNA noted in MNC in hepatitis |
Perkins et al. (131) | Mo, MNC | None | Immunoblot, RT-PCR, L-Arg to L-Cit | Yes | Increased L-Arg to L-Cit activity, NOS2 Ag, NOS2 mRNA in Mo and MNC from patients with RA; anti-TNF antibody treatment in vivo reduced the increased NOS activity and NOS2 Ag expression |
Tunctan et al. (119) | Mo | LPS | Nitrite; smooth muscle relaxation | Yes | 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 |
Wang et al. (120) | Alv Mac | None | Flow cytometry, immunohistology, nitrite | Yes | Higher NOS2 expression and nitrite production by cells from tuberculosis patients; nitrite production correlated significantly with exhaled NO concentration |