SUBJECT INDEX References to Figures and Tables are in italics aconitase EPR spectra of, Fig.14.1 inhibition by NO, 242 adenosine metabolism in influenza-infected mice, 283 adhesion molecules engagement of, in allograft rejection, 152 allograft rejection, 215, 221. See also transplantation completion of, 141 evaluation and monitoring of, 138-139, 150,214, by EPR, 146, 158,207, kinetics studies, 166, 170, 176, 207, Fig. 10.4-10. 6, 12.1-12.3 mechanisms of, 138, 169 alloantigen recognition, 146 of various organs, 173-177 of heart. See heart graft rejection of skin. See skin graft rejection systemic nature of, 140, 168 vascularization, 139, 166 allopeptide presentation by antigen-presenting cells, 146 animal tumors. See also cell lines delayed tumor development due to immunomodulation, 330 EPR signals of, 229-230, Fig.20.1 antisense oligonucleotides against adhesion molecules, in treatment of allograft rejection, 152 apoptosis, role of NO macrophage, 171,256 myocyte, 171 arachidonic acid metabolism engagement in chemokine action, 243 blood vessels adhesion of blood cells, 147, Fig.9.1. permeability enhanced by NO, 169, 289 brain (rat), postischemic NO distribution in, 120, 127-132 EPR image of, Fig. 7.6-7.9 calcium role in chemokine action, 243-244 cell lines EMRT-6, murine carcinoma induction of NO synthesis in, corresponding EPR signals, 233 fibroblasts (murine) NO synthesis in, 233 hepatocytes (rat) protective effects of NO, 174 L5178Y -R, murine lymphoma growth in various types of host, Fig. 20. 5 host-dependent intensity of ironnitrosyl EPR signals in, 318, Fig. 20.4 L929, murine fibroblasts resistance to NO-induced apoptosis, 257-260 P815, murine mastocytoma apoptosis induced by SNAP, 257 PROb, rat adenocarcinoma, 328 ambivalent role of NO in growth and immunotherapy of, 328-338 RAW 264.7, murine macrophages expression of NOS in, 270-272 apoptosis induced by SNAP, 257 RO-995, murine carcinoma EPR signals of, lymphokine action, 299-309, 342-343, Fig. 19. 1-19.4 Zeman UJ-90, gerbil melanoma tumor induction of iron-nitrosyl EPR signals in, 317-318 ceruloplasmin EPR signals of, in blood, 362, Fig.23.3 chemokines definition and classification of, 240 in cell migration, 244-246 receptors of, in leukocytes, 242-244 cholesterol, in dioleylphosphatidylcholine (DOpc) bilayers, NO permeability, 100-103, Fig.5.3-5.4, Tab.5.l
372 copper -dithiocarbamate (Cu-DETC), EPR spectra of, 63-64, 367, Fig. 3. 7, 23.7 dendritic cell migration, role of chemokines, 245-246 DEI'C. See iron-dithiocarbamates, copperdithiocarbamate dinitrosyl-iron. See iron-sulphurnitrosyl DNIC. See iron-sulphur-nitrosyl electron paramagnetic resonance, EPR, ESR, 38-42 detection of NO. See nitric oxide. See also iron-nitrosyl, signals of by spin-trapping. See nitric oxide, trapping detection of oxygen radicals. See oxygen radicals imaging. See electron paramagnetic resonance imaging in biological studies, 37, 314 in monitoring of heart rejection, 161, 206-210 signal of free radicals. See free radical electron paramagnetic resonance imaging, EPRI, 100-IIO, II6 3D, 113-115, Fig.6.3-6.4 gated, 115-116 image reconstruction, 123 of biological samples, 112-113 of NO distribution in brain, 120, 127-132 in isolated heart, 120-126 -iron-dithiocarbamates, 17 principles of, II 0-112 EPRI. See electron paramagnetic resonance imaging EPR. See electron paramagnetic resonance ESR. See electron paramagnetic resonance Fe-DETC2. See iron-dithiocarbamates Fe-MGD2. See iron-dithiocarbamates ferritin EPR ~ " p e cof, t rfig.14.1 a iron release from, by NO, 231 footprinting of NOS2 in RAW 264.7 cells, 272-273 free radical EPR signal, Fig.2.4 decrease after NAC treatment in normal tissue, 303 induction by IL-2 in normal tislme, 303, Fig.19.3 offusinite, line-broadening by NO, 16 of melanin in tumors, 315, 357, Fig.23.2 of metabolic origin, 191,303,315, 344, 358, Fig.22.1-22.3, 23.2 of solid carbon in human tumors, 359 role of, in carcinogenesis, Fig. 18. 12-18. 13 fusinite. See free radical, EPR signal gel-shift assay in studies on NOS2 transcriptional regulation, 270-271 glutathione level and neutralization of NO toxicity, 261 increase of, due to IL-2 and NAC treatment, 302 modulation of antitumor effects of IL-2 by, 296, 309 role in prevention of iron-sulphur center nitrosylation, 306 semiquinone EPR signal influenced by, 303 graft-versus-host disease, GvRD, 177, 214 impairment of, in Mongolian gerbils, 210 GSH level. See glutathione level GvRD. See graft-versus-host disease heart graft rejection, 138. See also allograft rejection, xenograft rejection acceleration of, 138, 205 and EPR signal of rejecting tissue, in a gerbil model, 207-209 in a murine model, 169, 191, Fig.10.6 in a "rat ear" model, 178 in a rat model, 164, 170,206 versus nitrate urine exretion, 170, 193 destruction of graft by inullunologic cells, 146 engagement of adhesion molecules in, 152 evaluation and monitoring of, 151, 158 graft arteriosclerosis, 138
373 Helicobacrer pylori infection ho&1 DNA damage as a result of, 278-279, Tab.18.l human tumors EPR signals detectable in, 297, 343-344, 353, Fig. 22. 1-22.3, attributed to free radicals 344, 357, 358, Fig.22.l-22.3, 23.2 attributed to iron-nitrosyl 344,362, Fig. 22. 1-22.3, 23.1, Tab. 23.2 the novel type of, quintets, 363, Fig.23.4, Tab.23.4 hydroxyl radical, OB, 42-45, 149 IFN -1'. See interferon-/, IL-l. See interleukin-l IL-2. See interleukin-2 immunotherapy of cancer EPR triplet signals in monitoring of progress of, 322-325 evolution of infiltrating lymphocytes, Fig.2l.8 regression of rat PROb adenocarcinoma due to NO production, 333-338 infections as a cause of cancer, 279-284, Fig. 18.13, Tab. 18.1 inhibitors of NO synthesis aminoguanidine, 171, 173-174 in rejecting grafts, 194, 216, Fig.n.1 N-monomethyl-L-arginine, L-NMMA, MLA pharmacological effects of, 194 N-nitro-L-arginine, L-NA, L-NNA, 318 methyl ester, L-NAME, 84-86 inos. See nitric oxide synthase interferon-/" IFN-/, induction of NO synthesis by, 229-234 in PROb tumor cells, 336-337 in influenza-infected mice 284 interleukin-i, IL-I IL-lll, in PROb tumor cells, 336-337 induction of NO synthesis, 233 interleukin-2, IL-2 antitumor effects, 296-302 increase of urine nitrate levels in mice 304 induction of inos in cancer patients, 296-297 iron -dithiocamamates, 61 as NO spin-traps, advantages and limitations, 69 in mononitrosyl-iron (MNIC) with NO, 62-68 in vivo usage, 63, 64-65 iron-dithiocamamate, Fe-DETC2, 16-17,62,68 iron-n-methyl-d-glucaminedithiocamamate, Fe-MGD2, 17,67-68 nitrosylation reactions 230-231 in murine tumors, detected by EPR, 342-343 iron-nitrosyl. See also iron-sulphurnitrosyl as a product of cell-mediated immune responses 190, 317-324, 342-343, 349, 362 EPR signals of, 284-285, 342-349, Fig. 22. 1-22.3 detectable during intestine transplantation, 177 in animal tumors, 298, 301, 306, 315, Fig. 20. 1 in blood of allograft host, 170 in co-cuitures 305-306 in ex vivo incubated heart muscle, 163 in human tumors, 344-349, 359-361, Fig. 22.1-22. 3, 23.2-23.3, Tab. 23. 2-23. 3, in mitochondria, 197 in rejecting heart grafts, 163, 191, 195, Fig.lO.3-lO.4, 11.1 its predictive value in the evaluation of tumor-host interactions, 321-322, Fig. 20. 4-20. 6 formation of, during oxidative stress 296, 303 induced in culture of human cell lines, 342-343 in human cancers, 344, 362 intracellular, 197,348-349 six and five coordinate 191, 199, 302, 343 iron-sulphur-nitrosyl, dinitrosyl-iron, DNIC, 49-51, 190, 299, 302, 303 EPR signals of, Fig.3.3 in mitochondria enzymes 197 in biological materials, Fig.3.1-3.2, 3.4-3.5
374 general properties of, 51-55 GSH prevention of the formation of, 306 in biological systems, 56, 59-60 in evaluation of NO synthesis, 55, 70 interactions, 57 with cysteine, 58-59 with serum albumin, 58 sodium nitroprusside transformation to, 60 ischemia/reperfusion injury in heart, 83, 85-91 engagement of adhesion molecules in, 152 EPR imaging of NO, Fig.6.2-6.4, 7.3-7.4 kinetics of NO production, Fig. 7.5 NO trapping during, 67-68, 120-121, 123-126, Fig.4.1-4.6 in rat brain 120, 127-132, Fig. 7.6-7.9 lipopolysaccharide, LPS EPR signal induction by of iron-dithiocarbamates, 55 of iron-nitrosyl, 315-318 L-NAME. See inhibitors of NO synthesis L-NA. See inhibitors of NO synthesis L-NMMA. See inhibitors of NO synthesis L-NNA. See inhibitors of NO synthesis loop-gap resonator design, 112 LPS. See lipopolysaccharide lymphocytes adhesion to endothelium during ischemia/reperfusion, 152 infiltration of rejecting allograft, 138-140 molecules engaged in the process of activation of, 147 tumor-infiltrating, TIL evolution of, during immunotherapy, Fig. 21.8 macrophages apoptosis of, induced by NO, 256 cytotoxicity of against neoplastic cells, 230, 231, 253-254,315-318,348,362 against rejecting graft 140, 150, 163, 207-210, 213, 218 impairment of, in Mongolian gerbils 210,315 rat splenic, stimulation of NO secretion with tumor cell supernatant, 336 tumor associated, 241-242 major histocompatibility complex class I and n, structure and expression, 146 role in graft immunogenicity, 139 MCP-l. See monocyte chemotactic protein-i melanin EPR signal of, in tumors 315,358, Fig.23.2 MGD. See iron-dithiocarbamates MHC, See major histocompatibility complex mitochondrium respiratory enzymes, 255 nitrosylation of, resulting EPR b'pectra 197,231 MLA. See inhibitors of NO synthesis MNIC. See iron-dithiocarbamates, mononitrosyl Mongolian gerbils, 209, 315 monocyte chemotactic protein-i, MCP-I, 241-242 expression in human tumor cell lines in vivo, 241 role in immunobiology of neoplastic tissues, 242 mononitrosyl-iron, MNIC. See also iron-dithiocarbamates stability of, 61 N-acetyl cysteine, NAC prevention of NO-mediated apoptosis, 261 NAC. See N-acetyl cysteine natural killer cells, NK chemokine action on, 245 impaired function of, in Mongolian gerbils, 210 necrosis of heart muscle corresponding EPR signals 164 due to heart rejection, 138 due to induced NO production, 171 NF-KB. See nuclear factor-kb nitrate, as a measure of NO production plasma or serum level, in human, 344-348 in rat, 158 urine level 158, 191, 193,214,296
375 nitric oxide, NO. See also nitrate, nitrite and air pollution, 5 and membranes, 95, 100 NO-penneability, 101-105, Fig. 5. 3-5.4, Tab.5.l binding to, Tab.1.l hemoglobin, 9-10, 15 in vivo targets, 12-14,230-233,301, 305-306, 348-349, Tab.l.2 metalloproteins, 9-I 4 spin traps, 15-17 transition metals, 8-9, detection of, by EPR, 7-8, 15-17. See also iron-nitrosyl by spin-label NO-metry 16, 95-100 in vivo 63, 64, 84 distribution of in ischemic brain, 120, 127-132 in isolated heart, 120-I 26 effect on DNA replication, 231 hypotheses on its role in interactions between different types of cells in tumor, 338 pathophysiological events, 234 in cross-regulation of enzymes, 13-14, Tab. 1.3-1.4 influence on vascular penneabiiity, 171, 289 in graft survival and rejection, 147, 194, 214 ambivalent role of, 221 influence on heart contractility, 172 kinetics of production, 220, Fig.10.4-l0.6, 12.1-12.3 inhibition of mitochondrial respiration by, 231,255, Tab. 11. 1-11.2 in invertebrates and vertebrates, 213 in tumor biology, 234, 289, 327-328 antitumor effects, 298-299, 321-322 chronic inhibition of its synthesis in tumors, 299 in carcinogenesis, 277-278 in human, 348 iron release by, from iron-containing proteins, 231, 232 production of, 3, 7, 62, 348. See also nitric oxide synthase during ischemia, 90 enzyme-independent, 84, 87-88, 161, Fig.4.3 in tumors. See iron-nitrosyl ph-dependence of, 88, Fig.4.4 reactions with oxygen radicals, 149, 284 suppresion of macropheagal function, 255-256 tumor infiltrating lymphocyte proliferation, 330 toxicity of, 5-7, 285-286, 288 against heart, 89-92 trapping, IS by hemoproteins, 155, 190-192, 195-199,205-207,209, 230-231,298,301-306, 315-317, 354, 357-361 by intracellular nonheme iron, 49, 55, 296, 298, 300-302 by iron-dithiocarbamates, 16-17, 55-57, 84, Fig.4.l, 7.2 in vitro 65-67, 84, 233 nitric oxide synthase, NOS, 213, 90. See also nitric oxide synthase inhibitors in ischemic heart, 84-86 inos, NOS2, NOS II high and low responders, 221 induction by IL-2, 295, 296-297 by influenza virus, 284 by OM 163 from E. coli, 334 organ-specific expression of, 175 switching off, 220 transcription, regulation of, 268-269 in human, 274 multi factor, 273-274 nitrite, as a measure of NO production in ischemic heart, 87-88 in skin xenografts ~ vivo, 216 plasma and serum level, in human, 344-348 in rat, 158 urine level, 158, 214, 344-348 nitroso-heme. See iron-nitrosyl nitrosonium ion, 52 nitroxides. in NO-metry, chemical structures of, Fig.5.2 interaction with NO, 16,95-96, 101-103 NK. See natural killer cells NO-hemoglobin. See also iron-nitrosyl in influenza-infected mice, 284-285 NOS. See nitric oxide synthase nuclear factor-kb, NF-KB regulation of NOS2 transcription, 270-272
376 oxidative stress -associated EPR signals, in nonnal tissue, 303 decrease of iron-nitrosyl complex formation by, 296 induced by IL-2 treatment, 296 modulation by thiols, 261, 296 oxygen radicals, EPR detection of, 45-47 by DMPO spin-trapping, 45-46, Fig.2.5 by rapid freezing technique, 46-47 OH radical, 45 generation of, 41-43, 149, Fig.18.2-18.3 in carcinogenesis 277-278, Fig.18.12-18.13 in lipid peroxidation, 44 reactions of, with nitric oxide 149, 284 PCR. See polymerase chain reaction peroxynitrite, 149, 284 inactivation of aconitase by, 232 tyrosine nitration in pathological events 285, Fig.18.12-18.13 phospholipase-a2, PLA2 role in chemokine action, 243-244 PLA2. See phospholipase-a2 polymerase chain reaction, PCR ligation-mediated, of NOS2 in RAW 264.7 cells, 272-273 proteolytic enzymes stimulation of the production of, by MCP-l,242 ribonucleotide reductase inhibition of. by NO, 231 skin graft rejection, 137 in anuran amphibians, 214 ex vivo studies, Fig. 13. 2 Smoluchowski equation, 96 spin label NO-metry. See nitric oxide, detection of, by spin-label NOmetry spin-trapping of NO. See nitric oxide, trapping of sponge matrix allograft model, 168, 214 superoxide ion, 41-45, Fig.18.2-18.3 in virus-infected mice 279-283 peroxynitrite generation, with NO, 149. 284 TIL. See lymphocytes TNF--y. See tumor necrosis factor-,/, transplantation. See also allograft rejection, xenograft rejection of heart, 168 development of surgical techniques, 159 heterotopic, 169 histopathologic grading of rejection, 159 retransplantation, 140 vascularized and non-vascularized animal models of, 166, 179 orthotopic, of intestine, 176 kidney, 177 liver, 174 lung, 173 triplet EPR signals. See iron-nitrosyl, EPR signals of tumor necrosis factor--y, TNF--y induction of NO synthesis, 233 tumors. See animal tumors, cell lines, human tumors xenograft rejection, 138, 168, 215, 220 evaluation and monitoring of, by EPR, 158,206