Heme Amplifies the Innate Immune Response to Microbial Molecules through Spleen Tyrosine Kinase (Syk)-dependent Reactive Oxygen Species Generation*

Name: Work Video:
Duration: 3 min 30 s
Patricia L. Fernández; Fabiano Ferreira; Letícia S. Alves; Rodrigo T. Figueiredo; Diego Mourão‐Sá; Guilherme B. Fortes; Sophie Bergstrand; David Lönn; Ricardo R. Cevallos; Renata M. Pereira; Ulisses Gazos Lopes; Leonardo H. Travassos; Cláudia N. Paiva; Marcelo T. Bozza
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1413, 1520, 1637, 1663, 1781, 2234, 2371, 2380, 2388, 2514, 2799, 2833, 2916, 3214, 3345, 3385], 'vivo': [55, 230, 1231], 'enhanced': [57, 232, 1461, 1609, 1795, 2133], 'cytokines': [61, 158, 236, 333, 1044, 1160, 1737, 3273, 3389], 'macrophages': [63, 238, 888, 1010, 1299, 1739, 2177, 3117, 3239], 'stimulated': [64, 239, 1740], 'with': [65, 240, 479, 572, 684, 1053, 1222, 1241, 1249, 1271, 1285, 1294, 1301, 1410, 1477, 1487, 1500, 1631, 1741, 2066, 2163, 2236, 2708, 2801, 2913, 3282], 'various': [66, 241], 'agonists': [67, 242, 1005, 1272, 3234], 'innate': [69, 244, 1372, 2537, 2555], 'immune': [70, 245, 1023, 1103, 1373, 3252, 3332], 'receptors.': [71, 246], 'Activation': [72, 247], 'nuclear': [74, 249], 'factor': [75, 250], 'κB': [76, 251], '(NF-κB)': [77, 252], 'MAPKs': [79, 254, 1297, 1615, 2138], 'generation': [82, 143, 257, 318, 1183, 1320, 1340, 1774, 2208, 2267, 2319, 3412], 'reactive': [84, 140, 259, 315, 994, 3223], 'oxygen': [85, 141, 260, 316, 579, 2808], 'species': [86, 142, 261, 317], 'were': [87, 262, 1188, 3417], 'essential': [88, 263, 1107, 1327, 1623, 3336], 'increase': [91, 266, 596, 1155, 1347, 1636, 2825, 3384], 'production': [94, 269, 987, 1158, 1229, 1283, 1349, 1415, 1674, 2123, 2217, 2225, 2477, 2533, 3216, 3387], 'plus': [98, 273], 'LPS.': [99, 274, 1170, 1254, 1304, 2480, 3399], 'This': [100, 275, 1099, 2544, 3328], 'synergistic': [101, 276, 998, 1176, 2119, 2174, 2192, 3227, 3405], 'effect': [102, 277, 739, 999, 1177, 1256, 1626, 1748, 1784, 2518, 2567, 2968, 3228, 3406], 'was': [107, 119, 282, 294, 1262, 1326, 1622, 1779], 'blocked': [108, 283], 'a': [110, 149, 285, 324, 375, 1153, 1250, 1362, 1660, 2164, 2328, 2374, 2431, 2466, 2491, 2500, 2515, 2549, 2604, 3382], 'selective': [111, 286, 979, 1632, 2165, 3208], 'inhibitor': [112, 287, 2166], 'spleen': [114, 289], 'tyrosine': [115, 290], 'kinase': [116, 291, 2231], '(Syk)': [117, 292], 'abrogated': [120, 295, 1310, 1634], 'dendritic': [122, 297, 890, 3119], 'cells': [123, 298, 891, 3120], 'deficient': [124, 299], 'Syk.': [126, 301], 'Moreover,': [127, 302, 1305, 1509], 'inhibition': [128, 303, 1306, 1798], 'Syk': [130, 305, 1192, 1382, 2159, 2168, 2189, 2197, 2370, 2435, 2510, 2574, 3421], 'downstream': [133, 308, 2199], 'PKC': [135, 310, 2202, 2311], 'PI3K': [137, 312, 2313], 'reduced': [138, 313], 'heme.': [145, 320], 'Our': [146, 321], 'results': [147, 322, 1360, 1472, 1583, 1808, 2221, 2524], 'highlight': [148, 323], 'mechanism': [150, 325, 1337, 2116, 2264, 2375, 2564], 'which': [152, 327, 2238], 'amplifies': [154, 329, 1587], 'triggered': [159, 334, 731, 1147, 1212, 2960, 3376], 'microbial': [161, 336, 935, 1051, 1149, 1163, 1214, 1223, 1650, 3164, 3280, 3378, 3392], 'molecule': [162, 337, 378, 2607], 'activation': [163, 338, 589, 783, 974, 1019, 1100, 1290, 1352, 1383, 1448, 1618, 1657, 1677, 1729, 2062, 2134, 2240, 2511, 2572, 2818, 3012, 3203, 3248, 3329], 'indicates': [165, 340, 2364], 'possible': [166, 341, 2467], 'pathways': [167, 342, 1309, 1443, 1506, 1621], 'for': [168, 343, 772, 1108, 1328, 1672, 3001, 3337], 'therapeutic': [169, 344], 'intervention': [170, 345], 'during': [171, 346], 'hemolytic': [172, 347], 'infectious': [173, 348, 354, 2583], 'diseases.': [174, 349], 'IntroductionA': [350, 2579], 'general': [351, 2550, 2580], 'consequence': [352, 2581], 'hemolysis,': [358, 2587], 'internal': [359, 2588], 'hemorrhage,': [360, 2589], 'or': [361, 406, 680, 1239, 1499, 1802, 2590, 2635, 2909], 'extensive': [362, 2591], 'cell': [363, 1534, 2592], 'damage': [364, 483, 1118, 2593, 2712, 3347], 'is': [365, 770, 877, 1045, 1105, 1112, 2270, 2484, 2528, 2570, 2594, 2999, 3106, 3274, 3334, 3341], 'release': [367, 373, 2596, 2602], 'hemeproteins.': [369, 2598], 'Upon': [370, 2599], 'oxidation,': [371, 2600], 'heme,': [374, 412, 569, 1628, 2603, 2641, 2798], 'potentially': [376, 2605], 'harmful': [377, 2606], '(1Ferreira': [379, 2608], 'A.': [380, 530, 545, 610, 612, 622, 650, 652, 664, 693, 1028, 1086, 1712, 1760, 1974, 1980, 2439, 2609, 2759, 2774, 2839, 2841, 2851, 2879, 2881, 2893, 2922, 3257, 3315], 'Balla': [381, 385, 542, 552, 613, 617, 2610, 2614, 2771, 2781, 2842, 2846], 'J.': [382, 389, 434, 449, 526, 543, 614, 716, 753, 855, 913, 1089, 1552, 1763, 1890, 1904, 1913, 1936, 1982, 1984, 1997, 2036, 2094, 2253, 2345, 2448, 2611, 2618, 2663, 2678, 2755, 2772, 2843, 2945, 2982, 3084, 3142, 3318], 'Jeney': [383, 615, 2612, 2844], 'V.': [384, 541, 616, 1978, 2613, 2770, 2845], 'G.': [386, 553, 618, 654, 1026, 1569, 1710, 1972, 2392, 2615, 2782, 2847, 2883, 3255], 'Soares': [387, 631, 665, 825, 2290, 2616, 2860, 2894, 3054], 'M.P.': [388, 632, 666, 826, 2291, 2617, 2861, 2895, 3055], 'Mol.': [390, 452, 2619, 2681], 'Med.': [391, 636, 1091, 1765, 1892, 1915, 1938, 2255, 2620, 2865, 3320], '2008;': [392, 1554, 1573, 2414, 2621], '86:': [393, 2622], '1097-1111Crossref': [394, 2623], 'PubMed': [395, 439, 457, 496, 537, 558, 640, 675, 706, 722, 762, 812, 836, 866, 924, 948, 968, 1035, 1070, 1127, 1557, 1576, 1684, 1704, 1719, 1875, 1896, 1919, 1942, 1954, 1989, 2019, 2052, 2110, 2146, 2259, 2301, 2356, 2422, 2459, 2624, 2668, 2686, 2725, 2766, 2787, 2869, 2904, 2935, 2951, 2991, 3041, 3065, 3095, 3153, 3177, 3197, 3264, 3299, 3356], 'Scopus': [396, 440, 458, 497, 559, 641, 676, 763, 813, 837, 867, 925, 949, 969, 1036, 1071, 1095, 1128, 1558, 1577, 1685, 1705, 1720, 1769, 1876, 1897, 1920, 1943, 1955, 1990, 2020, 2053, 2111, 2147, 2260, 2302, 2357, 2423, 2460, 2625, 2669, 2687, 2726, 2788, 2870, 2905, 2992, 3042, 3066, 3096, 3154, 3178, 3198, 3265, 3300, 3324, 3357], '(155)': [397, 2626], 'Google': [398, 442, 460, 499, 538, 561, 643, 678, 707, 723, 765, 815, 839, 869, 927, 951, 971, 1038, 1073, 1097, 1130, 1560, 1579, 1687, 1707, 1722, 1771, 1878, 1899, 1922, 1945, 1957, 1992, 2022, 2055, 2113, 2149, 2262, 2304, 2359, 2425, 2462, 2627, 2671, 2689, 2728, 2767, 2790, 2872, 2907, 2936, 2952, 2994, 3044, 3068, 3098, 3156, 3180, 3200, 3267, 3302, 3326, 3359], 'Scholar).': [399, 461, 500, 562, 724, 870, 972, 1039, 1098, 1131, 1580, 1723, 1772, 2056, 2114, 2150, 2305, 2360, 2426, 2628, 2690, 2729, 2791, 2953, 3099, 3201, 3268, 3327, 3360], 'Heme-binding': [400, 2629], 'plasma': [401, 467, 2382, 2630, 2696], 'proteins,': [402, 2631], 'such': [403, 1058, 2632, 3287], 'as': [404, 1059, 1539, 2633, 3288], 'hemopexin': [405, 2634], 'albumin,': [407, 2636], 'remove': [408, 2637], 'intravascular': [410, 2639], 'free': [411, 427, 2640, 2656], 'subsequently': [413, 2642], 'degraded': [414, 2643], 'oxygenase-1': [417, 2646], '(HO-1),': [418, 2647], 'generating': [419, 2648], 'equimolar': [420, 2649], 'amounts': [421, 504, 2650, 2733], 'biliverdin,': [423, 2652], 'carbon': [424, 2653], 'monoxide,': [425, 2654], 'iron': [428, 2657], '(2Muller-Eberhard': [429, 2658], 'U.': [430, 524, 2659, 2753], 'Fraig': [431, 2660], 'M.': [432, 532, 628, 714, 1935, 1964, 2661, 2761, 2857, 2943], 'Am.': [433, 448, 2662, 2677], 'Hematol.': [435, 2664], '1993;': [436, 2665], '42:': [437, 2666], '59-62Crossref': [438, 2667], '(67)': [441, 2670], 'Scholar,': [443, 539, 644, 708, 816, 840, 952, 1074, 1561, 1688, 1708, 1879, 1900, 1923, 1946, 1958, 1993, 2023, 2672, 2768, 2873, 2937, 3045, 3069, 3181, 3303], '3Morse': [444, 2673], 'D.': [445, 701, 710, 822, 2287, 2674, 2930, 2939, 3051], 'Choi': [446, 2675], 'A.M.': [447, 2676], 'Respir.': [450, 2679], 'Cell': [451, 2008, 2680], 'Biol.': [453, 856, 914, 2346, 2449, 2682, 3085, 3143], '2002;': [454, 555, 759, 809, 1067, 1124, 2683, 2784, 2988, 3038, 3296, 3353], '27:': [455, 2684], '8-16Crossref': [456, 2685], '(442)': [459, 2688], 'HO-1-deficient': [462, 2691], 'mice': [463, 2692], '(Hmox−/−)': [464, 2693], 'have': [465, 873, 1745, 2694, 3102], 'high': [466, 1201, 2067, 2695], 'concentrations': [468, 2697], 'susceptibility': [474, 2703], 'LPS-induced': [476, 1786, 2705], 'lethality,': [477, 2706], 'associated': [478, 683, 1532, 2707, 2912], 'inflammation': [480, 522, 2709, 2751], 'oxidative': [482, 519, 1322, 2711, 2748], '(4Poss': [484, 2713], 'K.D.': [485, 2714], 'Tonegawa': [486, 2715], 'S.': [487, 620, 630, 658, 699, 747, 954, 956, 1690, 1692, 1857, 1887, 1912, 1970, 1999, 2250, 2445, 2716, 2849, 2859, 2887, 2928, 2976, 3183, 3185], 'Proc.': [488, 667, 2717, 2896], 'Natl.': [489, 668, 2718, 2897], 'Acad.': [490, 669, 2719, 2898], 'Sci.': [491, 670, 2720, 2899], 'U.S.A.': [492, 671, 2721, 2900], '1997;': [493, 719, 2722, 2948], '94:': [494, 2723], '10925-10930Crossref': [495, 2724], '(1100)': [498, 2727], 'Accumulation': [501, 2730], 'large': [503, 2732], 'might': [507, 2736], 'overwhelm': [508, 2737], 'capacity': [510, 2739], 'scavengers': [513, 2742], 'degrading': [515, 2744], 'system,': [516, 2745], 'thus': [517, 1418, 2325, 2464, 2746], 'causing': [518, 2747], 'stress': [520, 1323, 2749], '(5Muller-Eberhard': [523, 2752], 'Javid': [525, 2754], 'Liem': [527, 2756], 'H.H.': [528, 2757], 'Hanstein': [529, 2758], 'Hanna': [531, 2760], 'Blood.': [533, 554, 808, 2762, 2783, 3037], '1968;': [534, 2763], '32:': [535, 2045, 2103, 2764], '811-815Crossref': [536, 2765], '6Jeney': [540, 2769], 'Yachie': [544, 2773], 'Varga': [546, 2775], 'Z.': [547, 2776], 'Vercellotti': [548, 2777], 'G.M.': [549, 2778], 'Eaton': [550, 754, 2779, 2983], 'J.W.': [551, 755, 2780, 2984], '100:': [556, 2785], '879-887Crossref': [557, 2786], '(501)': [560, 2789], 'fact,': [564, 2793], 'recent': [565, 2362, 2794], 'studies': [566, 1825, 2795], 'suggest': [567, 1809, 2796], 'combination': [571, 1602, 2800], 'ROS': [573, 790, 1063, 1185, 1339, 1654, 1776, 1811, 2210, 2224, 2266, 2318, 2577, 2802, 3019, 3292, 3414], '3The': [574, 2803], 'abbreviations': [575, 2804], 'used': [576, 2805], 'are:': [577, 2806], 'ROSreactive': [578, 2807], 'speciesDCdendritic': [580, 2809], 'cellDPIdiphenyleneiodoniumNACN-acetyl-l-cysteineTLRToll-like': [581, 2810], 'receptorsPRRpattern': [582, 2811], 'recognition': [583, 930, 2812, 3159], 'receptorCM-H2DCFDA5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein': [584, 2813], 'diacetate,': [585, 2814], 'acetyl': [586, 2815], 'esterITAMimmunoreceptor': [587, 2816], 'tyrosine-based': [588, 2817], 'motifNODnucleotide-binding': [590, 2819], 'oligomerization': [591, 2820], 'domain.': [592, 2821], 'mediators,': [595, 992, 2824, 3221], 'blood': [597, 2826], 'brain': [598, 2827], 'barrier': [599, 2828], 'leakage': [600, 2829], 'hepatocyte': [602, 2831], 'necrosis': [603, 2832], 'models': [605, 2834], 'malarial': [607, 2836], 'infection': [608, 2837], '(7Pamplona': [609, 2838], 'Ferreira': [611, 651, 2840, 2880], 'Epiphanio': [619, 2848], 'Chora': [621, 649, 2850, 2878], 'Rodrigues': [623, 2852], 'C.D.': [624, 2853], 'Gregoire': [625, 2854], 'I.P.': [626, 2855], 'Cunha-Rodrigues': [627, 2856], 'Portugal': [629, 2858], 'Mota': [633, 2862], 'M.M.': [634, 2863], 'Nat.': [635, 1029, 1713, 1949, 2141, 2864, 3258], '2007;': [637, 858, 916, 945, 1032, 1681, 1716, 2348, 2866, 3087, 3145, 3174, 3261], '13:': [638, 2867], '703-710Crossref': [639, 2868], '(419)': [642, 2871], '8Seixas': [645, 2874], 'E.': [646, 691, 1853, 1976, 2875, 2920], 'Gozzelino': [647, 2876], 'R.': [648, 656, 943, 1679, 2877, 2885, 3172], 'Silva': [653, 2882], 'Larsen': [655, 2884], 'Rebelo': [657, 2886], 'Penido': [659, 2888], 'C.': [660, 805, 1065, 1122, 1865, 1966, 2889, 3034, 3294, 3351], 'Smith': [661, 2890], 'N.R.': [662, 2891], 'Coutinho': [663, 2892], '2009;': [672, 1951, 1986, 2011, 2143, 2901], '106:': [673, 2902], '15837-15842Crossref': [674, 2903], '(213)': [677, 2906], 'Scholar).Hemolysis': [679, 2908], 'hemoglobinemia': [681, 2910], 'mortality': [686, 2915], 'septic': [688, 1199, 2917], 'patients': [689, 2918], '(9Griffiths': [690, 2919], 'Cortes': [692, 2921], 'Gilbert': [694, 2923], 'N.': [695, 1968, 2924], 'Stevenson': [696, 2925], 'P.': [697, 2926], 'MacDonald': [698, 2927], 'Pepper': [700, 2929], 'Lancet.': [702, 2931], '1995;': [703, 2932], '345:': [704, 2933], '158-160Abstract': [705, 2934], '10Su': [709, 2938], 'Roth': [711, 752, 2940, 2981], 'R.I.': [712, 2941], 'Yoshida': [713, 2942], 'Levin': [715, 2944], 'Infect.': [717, 2946], 'Immun.': [718, 2947], '65:': [720, 2949], '1258-1266Crossref': [721, 2950], 'Hemoglobin': [725, 2954], 'increases': [726, 1733, 2955], 'TNF': [730, 886, 2959, 3115], 'LPS,': [733, 1266, 1742, 2962], 'whereas': [734, 1403, 1743, 1797, 2075, 2963], 'globin': [735, 2964], 'has': [736, 777, 2058, 2965, 3006], 'an': [737, 1244, 1286, 1608, 1746, 1827, 2132, 2966], 'inhibitory': [738, 1747, 2967], '(11Yang': [740, 2969], 'H.': [741, 743, 749, 1962, 2970, 2972, 2978], 'Wang': [742, 748, 2971, 2977], 'Bernik': [744, 2973], 'T.R.': [745, 2974], 'Ivanova': [746, 2975], 'Ulloa': [750, 2979], 'L.': [751, 2025, 2029, 2083, 2087, 2980], 'Tracey': [756, 2985], 'K.J.': [757, 2986], 'Shock.': [758, 2987], '17:': [760, 2989], '485-490Crossref': [761, 2990], '(31)': [764, 2993], 'Scholar),': [766, 2463, 2995], 'suggesting': [767, 1419, 2327, 2465, 2996], 'responsible': [771, 3000], 'amplification.': [775, 3004], 'Heme': [776, 1151, 1433, 1459, 3005, 3380], 'several': [778, 1831, 3007], 'pro-inflammatory': [779, 3008], 'activities,': [780, 3009], 'including': [781, 2201, 3010], 'leukocyte': [782, 3011], 'migration,': [785, 3014], 'up-regulation': [786, 3015], 'adhesion': [788, 3017], 'molecules,': [789, 3018], 'production,': [791, 3020], 'induction': [793, 2120, 3022], 'expression': [796, 3025], '(12Graça-Souza': [797, 3026], 'A.V.': [798, 852, 910, 2342, 3027, 3081, 3139], 'Arruda': [799, 3028], 'M.A.': [800, 1849, 3029], 'de': [801, 3030], 'Freitas': [802, 3031], 'M.S.': [803, 3032], 'Barja-Fidalgo': [804, 3033], 'Oliveira': [806, 905, 907, 3035, 3134, 3136], 'P.L.': [807, 846, 896, 908, 2336, 3036, 3075, 3125, 3137], '99:': [810, 3039], '4160-4165Crossref': [811, 3040], '(222)': [814, 3043], '13Wagener': [817, 3046], 'F.A.': [818, 2283, 3047], 'Volk': [819, 2284, 3048], 'H.D.': [820, 2285, 3049], 'Willis': [821, 2286, 3050], 'Abraham': [823, 2288, 3052], 'N.G.': [824, 2289, 3053], 'Adema': [827, 2292, 3056], 'G.J.': [828, 2293, 3057], 'Figdor': [829, 2294, 3058], 'C.G.': [830, 2295, 3059], 'Pharmacol.': [831, 2296, 3060], 'Rev.': [832, 1030, 1714, 2297, 3061, 3259], '2003;': [833, 1893, 1916, 2256, 2298, 2451, 3062], '55:': [834, 2299, 3063], '551-571Crossref': [835, 2300, 3064], '(465)': [838, 2303, 3067], '14Porto': [841, 3070], 'B.N.': [842, 900, 1881, 2244, 2332, 3071, 3129], 'Alves': [843, 903, 2333, 3072, 3132], 'L.S.': [844, 904, 2334, 3073, 3133], 'Fernández': [845, 2335, 3074], 'Dutra': [847, 901, 2337, 3076, 3130], 'T.P.': [848, 2338, 3077], 'Figueiredo': [849, 2339, 3078], 'R.T.': [850, 894, 2340, 3079, 3123], 'Graça-Souza': [851, 909, 2341, 3080, 3138], 'Bozza': [853, 911, 2343, 3082, 3140], 'M.T.': [854, 912, 2344, 3083, 3141], 'Chem.': [857, 915, 2347, 2450, 3086, 3144], '282:': [859, 917, 2349, 3088, 3146], '24430-24436Abstract': [860, 2350, 3089], 'Full': [861, 863, 919, 921, 963, 965, 1699, 1701, 1870, 1872, 2014, 2016, 2047, 2049, 2105, 2107, 2351, 2353, 2417, 2419, 2454, 2456, 3090, 3092, 3148, 3150, 3192, 3194], 'Text': [862, 864, 920, 922, 964, 966, 1700, 1702, 1871, 1873, 2015, 2017, 2048, 2050, 2106, 2108, 2352, 2354, 2418, 2420, 2455, 2457, 3091, 3093, 3149, 3151, 3193, 3195], 'PDF': [865, 923, 967, 1703, 1874, 2018, 2051, 2109, 2355, 2421, 2458, 3094, 3152, 3196], '(119)': [868, 2358, 3097], 'Recently,': [871, 3100], 'shown': [874, 3103], 'able': [878, 1141, 1502, 3107, 3370], 'activate': [880, 2369, 2494, 3109], 'Toll-like': [881, 3110], 'receptor': [882, 1676, 2492, 2504, 3111], '4': [883, 3112], '(TLR4)': [884, 3113], 'inducing': [885, 3114], 'on': [887, 1006, 1178, 1191, 1259, 1298, 1593, 1785, 1819, 2176, 2190, 2215, 2278, 2317, 2323, 2386, 2434, 2472, 2475, 2552, 3116, 3235, 3407, 3420], '(DC)': [892, 3121], '(15Figueiredo': [893, 3122], 'Fernandez': [895, 3124], 'Mourao-Sa': [897, 3126], 'D.S.': [898, 3127], 'Porto': [899, 3128], 'F.F.': [902, 3131], 'M.F.': [906, 3135], '20221-20229Abstract': [918, 3147], '(392)': [926, 3155], 'Scholar).Mammalian': [928, 3157], 'pattern': [929, 3158], 'receptors': [931, 977, 2065, 2128, 2379, 2538, 3160, 3206], '(PRRs)': [932, 3161], 'recognize': [933, 3162], 'conserved': [934, 3163], 'from': [937, 1055, 3166, 3284], 'all': [938, 2205, 3167], 'classes': [939, 3168], 'microorganisms': [941, 3170], '(16Medzhitov': [942, 1678, 3171], 'Nature.': [944, 1066, 1123, 1680, 1985, 3173, 3295, 3352], '449:': [946, 1682, 3175], '819-826Crossref': [947, 1683, 3176], '(1966)': [950, 1686, 3179], '17Akira': [953, 1689, 3182], 'Uematsu': [955, 1691, 3184], 'Takeuchi': [957, 1693, 3186], 'O.': [958, 1694, 1851, 1960, 3187], 'Cell.': [959, 1695, 3188], '2006;': [960, 1092, 1696, 1766, 3189, 3321], '124:': [961, 1697, 3190], '783-801Abstract': [962, 1698, 3191], '(8561)': [970, 1706, 3199], 'The': [973, 997, 1040, 1255, 1280, 1335, 1617, 1640, 1773, 2115, 2194, 2497, 2562, 3202, 3226, 3269], 'elicits': [978, 3207], 'intracellular': [980, 3209], 'signaling': [981, 1378, 1667, 3210], 'cascades': [982, 3211], 'result': [984, 3213], 'cytokines,': [989, 1060, 1417, 3218, 3289], 'chemokines,': [990, 3219], 'lipid': [991, 2389, 3220], 'oxygen/nitrogen': [995, 3224], 'species.': [996, 3225], 'certain': [1001, 3230], 'associations': [1002, 3231], 'PRR': [1004, 3233], 'DC': [1012, 2372, 3241], 'promotes': [1013, 3242], 'adaptive': [1022, 3251], 'system': [1024, 1104, 3253, 3333], '(18Trinchieri': [1025, 3254], 'Sher': [1027, 1711, 3256], 'Immunol.': [1031, 1572, 1715, 1950, 2142, 3260], '7:': [1033, 1717, 3262], '179-190Crossref': [1034, 1718, 3263], '(1065)': [1037, 1721, 3266], 'also': [1046, 1113, 1269, 1460, 2315, 2326, 2428, 3275, 3342], 'achieved': [1047, 3276], 'combinations': [1049, 3278], 'host': [1056, 3285], 'origin': [1057, 3286], 'ATP,': [1061, 3290], '(19Nathan': [1064, 1121, 3293, 3350], '420:': [1068, 1125, 3297, 3354], '846-852Crossref': [1069, 1126, 3298, 3355], '(1980)': [1072, 1129, 3301, 3358], '20Powers': [1075, 3304], 'K.A.': [1076, 1750, 2007, 3305], 'Szászi': [1077, 1751, 3306], 'K.': [1078, 1752, 2001, 2394, 3307], 'Khadaroo': [1079, 1753, 3308], 'R.G.': [1080, 1754, 3309], 'Tawadros': [1081, 1755, 3310], 'P.S.': [1082, 1756, 3311], 'Marshall': [1083, 1757, 1909, 3312], 'J.C.': [1084, 1758, 3313], 'Kapus': [1085, 1759, 3314], 'Rotstein': [1087, 1761, 3316], 'O.D.': [1088, 1762, 3317], 'Exp.': [1090, 1764, 1891, 1914, 1937, 2254, 3319], '8:': [1093, 1767, 3322], '1951-1961Crossref': [1094, 1768, 3323], '(152)': [1096, 1770, 3325], 'considered': [1106, 2271, 3335], 'pathogen': [1109, 3338], 'killing': [1110, 3339], 'critically': [1114, 3343], 'involved': [1115, 1350, 1780, 1818, 2316, 3344], 'tissue': [1117, 3346], 'sepsis': [1120, 3349], 'this': [1133, 1421, 1794, 2470, 2495, 2566, 3362], 'study,': [1134, 3363], 'investigated': [1136, 3365], 'if': [1137, 3366], 'would': [1139, 3368], 'affect': [1143, 1655, 3372], 'molecules.': [1150, 1215, 3379], 'caused': [1152, 1243, 1607, 2155, 2169, 3381], 'remarkable': [1154, 3383], 'We': [1171, 2151, 3400], 'demonstrate': [1172, 3401], 'heme-LPS': [1175, 1344, 1820, 2173, 2191, 2213, 3404], 'both': [1189, 1505, 1837, 3418], 'dependent': [1190, 2277, 2385, 2433, 3419], 'activation.DISCUSSIONIn': [1193], 'malaria,': [1194], 'hemorrhagic': [1195], 'fevers,': [1196], 'leptospirosis,': [1197], 'shock,': [1200], 'quantities': [1202], 'hemoproteins': [1204], 'probably': [1207], 'affecting': [1208, 1376], 'showed': [1218], 'synergized': [1221], 'products': [1224], 'vitro.': [1234], 'Hemolysis': [1235], 'phenylhydrazine': [1238], 'treatment': [1240, 1630, 2162], 'when': [1247], 'combined': [1248], 'sublethal': [1251], 'dose': [1252, 1394, 1406], 'not': [1263], 'restricted': [1264], 'synergizes': [1270, 1476], 'TLR2,': [1274, 1466, 2237], 'TLR3,': [1275], 'TLR9,': [1276, 1467], 'NOD1,': [1277], 'NOD2.': [1279], 'correlated': [1284], 'earlier': [1287], 'heightened': [1289], 'NF-κB': [1292, 1612, 1731, 2136, 2242, 2560], 'phosphorylation': [1295, 2157], 'treated': [1300], 'TNF.': [1315], 'Furthermore,': [1316], 'demonstrated': [1318, 1826], 'its': [1329], 'potentiating': [1330, 1783, 2531], 'effects': [1331, 2175], 'upon': [1332, 1447, 1675], 'stimulation.': [1334], 'upstream': [1336], 'synergism': [1345, 1422, 1821, 2214, 2474], 'Syk,': [1354], 'PI3K,': [1355, 2204], 'PKC.': [1357], 'Together,': [1358, 1581], 'revealed': [1361], 'critical': [1363, 2186], 'previously': [1365], 'unrecognized': [1366], 'role': [1367, 2187, 2551], 'enhancing': [1371], 'PRRs': [1380, 1591, 1832], 'through': [1381], 'subsequent': [1385, 2576], 'change': [1386], 'redox': [1389, 1641], 'state': [1390, 1642], 'macrophages.A': [1392], 'low': [1393, 1430, 2076], 'alone': [1397], 'resulted': [1398, 1412], 'insignificant': [1400], 'secretion,': [1402], 'same': [1405], 'together': [1409], 'substantial': [1414], 'may': [1423], 'particularly': [1425], 'important': [1426], 'under': [1427], 'conditions': [1428], 'agonist': [1431], 'concentrations.': [1432], 'affected': [1434, 2206], 'MyD88': [1435, 1483], 'TIR': [1437, 1492], 'domain-containing': [1438, 1493], 'adaptor-inducing': [1439, 1494], 'interferon': [1440, 1495], 'β': [1441, 1496], '(TRIF)': [1442], 'TLR4,': [1450], 'increasing': [1451], 'TNF,': [1455], 'IL-6,': [1456], 'IP-10.': [1458], 'TLR3': [1469], 'agonists.': [1470, 1517], 'These': [1471, 1518, 1807, 2220], 'indicate': [1473], 'those': [1478], 'TLRs': [1479, 2125], 'use': [1481, 1537], 'exclusively': [1482], '(TLR2': [1484], '-9),': [1486], 'TLR': [1489, 1664, 2073], 'activates': [1491, 2429], 'only': [1497], '(TLR3),': [1498], 'induce': [1504], 'simultaneously': [1507], '(TLR4).': [1508], 'NOD': [1516], 'receptors,': [1519, 1835, 2074], 'contrast': [1521], 'TLRs,': [1523], 'localized': [1525], 'cytosol,': [1528], 'instead': [1529], 'being': [1531], 'membranes,': [1535], 'RICK/RIP2': [1538], 'adaptor': [1540], 'protein': [1541, 2378], '(30Carneiro': [1542], 'L.A.': [1543, 2400], 'Magalhaes': [1544], 'J.G.': [1545], 'Tattoli': [1546], 'I.': [1547], 'Philpott': [1548], 'D.J.': [1549], 'Travassos': [1550], 'L.H.': [1551], 'Pathol.': [1553], '214:': [1555], '136-148Crossref': [1556], '(151)': [1559], '31Shaw': [1562], 'M.H.': [1563], 'Reimer': [1564], 'T.': [1565, 1929, 2404], 'Kim': [1566], 'Y.G.': [1567], 'Nuñez': [1568], 'Curr.': [1570], 'Opin.': [1571], '20:': [1574], '377-382Crossref': [1575], '(238)': [1578], 'establish': [1584], 'situated': [1592], 'distinct': [1594, 1598], 'locations': [1595], 'using': [1597], 'signal': [1599, 2233], 'transduction': [1600], 'pathways.The': [1601], 'IκBα': [1610], 'degradation,': [1611], 'activation,': [1613], 'phosphorylation.': [1616], 'inhibitors': [1633, 2195], 'secretion.': [1639, 1788], 'severely': [1643], 'leukocytes': [1648], 'cytokines.': [1653], 'NF-κB,': [1659, 2430], 'key': [1661], 'component': [1662], 'NLR': [1666], 'pathways,': [1668], 'required': [1671], '18Trinchieri': [1709], 'Exogenously': [1724], 'added': [1725], 'H2O2': [1726, 2427, 2489], 'causes': [1727, 2070], 'antioxidants': [1744], '(20Powers': [1749], 'NAC,': [1789], 'DPI,': [1790], 'rotenone': [1792], 'impaired': [1793], 'response,': [1796], 'xanthine': [1800], 'oxidase': [1801], 'NOS': [1803], 'had': [1804], 'no': [1805, 2485], 'effect.': [1806], 'generated': [1812], 'NADPH': [1814], 'mitochondria': [1816], 'produce': [1823], 'cytokines.Recent': [1824], 'intense': [1828], 'cooperation': [1829, 2235], 'ITAM-associated': [1834, 2064, 2127, 2503], 'demonstrating': [1836], 'positive': [1838], 'negative': [1840], 'regulation': [1841], '(22Rogers': [1842], 'N.C.': [1843], 'Slack': [1844], 'E.C.': [1845], 'Edwards': [1846], 'A.D.': [1847], 'Nolte': [1848], 'Schulz': [1850], 'Schweighoffer': [1852, 1975], 'Williams': [1854, 1905], 'D.L.': [1855, 1906], 'Gordon': [1856, 1911, 2026, 2084], 'Tybulewicz': [1858, 1977], 'V.L.': [1859], 'Brown': [1860, 2004], 'G.D.': [1861, 1902, 2005, 2040, 2098], 'Reis': [1862], 'e': [1863], 'Sousa': [1864], 'Immunity.': [1866, 2043, 2101, 2413], '2005;': [1867, 1939], '22:': [1868], '507-517Abstract': [1869], '(725)': [1877], '26Gantner': [1880], 'Simmons': [1882, 2245], 'R.M.': [1883, 2246], 'Canavera': [1884, 2247], 'S.J.': [1885, 2248], 'Akira': [1886, 2249], 'Underhill': [1888, 2251], 'D.M.': [1889, 2252], '197:': [1894, 1917, 2257], '1107-1117Crossref': [1895, 2258], '(1309)': [1898, 2261], '27Brown': [1901], 'Herre': [1903], 'Willment': [1907], 'J.A.': [1908], 'A.S.': [1910], '1119-1124Crossref': [1918], '(983)': [1921], '28Turnbull': [1924], 'I.R.': [1925], 'McDunn': [1926], 'J.E.': [1927], 'Takai': [1928], 'Townsend': [1930], 'R.R.': [1931], 'Cobb': [1932], 'J.P.': [1933], 'Colonna': [1934], '202:': [1940], '363-369Crossref': [1941], '(79)': [1944], '29Ivashkiv': [1947], 'L.B.': [1948, 2042, 2100, 2140], '10:': [1952, 2144], '340-347Crossref': [1953, 2145], '(174)': [1956, 2148], '32Gross': [1959], 'Poeck': [1961], 'Bscheider': [1963], 'Dostert': [1965], 'Hannesschläger': [1967], 'Endres': [1969], 'Hartmann': [1971], 'Tardivel': [1973], 'Mocsai': [1979], 'Tschopp': [1981], 'Ruland': [1983], '459:': [1987], '433-436Crossref': [1988], '(684)': [1991], '33Hise': [1994], 'A.G.': [1995], 'Tomalka': [1996], 'Ganesan': [1998], 'Patel': [2000], 'Hall': [2002], 'B.A.': [2003], 'Fitzgerald': [2006], 'Host': [2009], 'Microbe.': [2010], '5:': [2012], '487-497Abstract': [2013], '(434)': [2021], '34Wang': [2024], 'R.A.': [2027, 2085], 'Huynh': [2028, 2086], 'Su': [2030, 2088], 'X.': [2031, 2089], 'Park': [2032, 2090], 'Min': [2033, 2091], 'K.H.': [2034, 2092], 'Han': [2035, 2093], 'Arthur': [2037, 2095], 'J.S.': [2038, 2096], 'Kalliolias': [2039, 2097], 'Ivashkiv': [2041, 2099], '2010;': [2044, 2102], '518-530Abstract': [2046, 2104], '(112)': [2054, 2112], 'It': [2057], 'been': [2059], 'suggested': [2060], 'affinity': [2068, 2077], 'ligands': [2069, 2078], 'cross-inhibition': [2071], 'potentiate': [2079], '(34Wang': [2082], 'seems': [2129], '(29Ivashkiv': [2139], 'observed': [2152, 2309], 'abrogation': [2171], 'DC.': [2179], 'Using': [2180], 'Syk-deficient': [2181], 'DC,': [2182], 'confirmed': [2184], 'effects.': [2193], 'effectors,': [2200], 'macrophages.': [2219], 'resemble': [2222], 'Dectin-1': [2228], 'TGF-β-activated': [2230], '(TAK1)-mediated': [2232], 'enhances': [2239], '(26Gantner': [2243], 'Scholar).The': [2263], 'at': [2274], 'least': [2275], 'partially': [2276], 'Fenton': [2280], 'reaction': [2281], '(13Wagener': [2282], 'However,': [2306], 'recently': [2308], 'neutrophils,': [2324], 'receptor-mediated': [2329], 'process': [2330, 2432], '(14Porto': [2331], 'A': [2361], 'report': [2363], 'monosodium': [2366], 'urate': [2367], 'crystals': [2368], 'independent': [2376], 'membrane': [2383, 2516], 'cholesterol': [2387], 'rafts': [2390], '(35Ng': [2391], 'Sharma': [2393], 'Ward': [2395], 'S.M.': [2396], 'Desrosiers': [2397], 'M.D.': [2398], 'Stephens': [2399], 'Schoel': [2401], 'W.M.': [2402], 'Li': [2403], 'Lowell': [2405], 'C.A.': [2406], 'Ling': [2407], 'C.C.': [2408], 'Amrein': [2409], 'M.W.': [2410], 'Shi': [2411], 'Y.': [2412, 2437], '29:': [2415], '807-818Abstract': [2416], '(219)': [2424], '(36Takada': [2436], 'Mukhopadhyay': [2438], 'Kundu': [2440], 'G.C.': [2441], 'Mahabeleshwar': [2442], 'G.H.': [2443], 'Singh': [2444], 'Aggarwal': [2446], 'B.B.': [2447], '278:': [2452], '24233-24241Abstract': [2453], '(394)': [2461], 'involvement': [2468, 2498], 'pathway': [2471], 'H2O2-induced': [2473], 'At': [2481], 'present': [2482], 'there': [2483], 'evidence': [2486], 'indicating': [2487], 'uses': [2490], 'pathway.': [2496], 'putative': [2501], 'specific': [2502], 'activated': [2505], 'or,': [2508], 'alternatively,': [2509], 'receptor-independent': [2517], 'requires': [2519], 'further': [2520], 'investigation.In': [2521], 'conclusion,': [2522], 'our': [2523], 'capable': [2529], 'different': [2536], 'irrespective': [2539], 'their': [2541], 'subcellular': [2542], 'localization.': [2543], 'phenomenon': [2545], 'ascribes': [2546], 'modulation': [2553], 'responses': [2556], 'pathogens': [2558], 'activation.': [2561, 3422], 'molecular': [2563], 'behind': [2565], 'generation.': [2578]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W1972389070', 'counts_by_year': [{'year': 2024, 'cited_by_count': 4}, {'year': 2023, 'cited_by_count': 4}, {'year': 2022, 'cited_by_count': 6}, {'year': 2021, 'cited_by_count': 6}, {'year': 2020, 'cited_by_count': 12}, {'year': 2019, 'cited_by_count': 10}, {'year': 2018, 'cited_by_count': 6}, {'year': 2017, 'cited_by_count': 6}, {'year': 2016, 'cited_by_count': 9}, {'year': 2015, 'cited_by_count': 7}, {'year': 2014, 'cited_by_count': 6}, {'year': 2013, 'cited_by_count': 5}, {'year': 2012, 'cited_by_count': 7}], 'updated_date': '2024-12-24T05:59:43.560130', 'created_date': '2016-06-24'}
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