CoChat
Sign Up
Cited by 55Gastrointestinal motility and disordersHeme Oxygenase-1 and Carbon MonoxideCongenital gastrointestinal and neural anomalies

Macrophages in diabetic gastroparesis – the missing link?

Open access
Neshatian, L., Gibbons, S. J., Farrugia, G.·2015·Neurogastroenterology & Motility
DOI 10.1111/nmo.12418PMC PMC4409126
Open this paper in CoChat — free account

Abstract

Background: Diabetic gastroparesis results in significant morbidity for patients and major economic burden for society. Treatment options for diabetic gastroparesis are currently directed at symptom control rather than the underlying disease and are limited. The pathophysiology of diabetic gastroparesis includes damage to intrinsic and extrinsic neurons, smooth muscle, and interstitial cells of C ajal ( ICC ). Oxidative damage in diabetes appears to be one of the primary insults involved in the pathogenesis of several complications of diabetes, including gastroparesis. Recent studies have highlighted the potential role of macrophages as key cellular elements in the pathogenesis of diabetic gastroparesis. Macrophages are important for both homeostasis and defense against a variety of pathogens. Heme oxygenase 1 ( HO 1), an enzyme expressed in a subset of macrophages has emerged as a major protective mechanism against oxidative stress. Activation of macrophages with high levels of HO 1 expression protects against development of delayed gastric emptying in animal models of diabetes, while activation of macrophages that do not express HO 1 are linked to neuromuscular cell injury. Targeting macrophages and HO 1 may therefore be a therapeutic option in diabetic gastroparesis. Purpose: This report briefly reviews the pathophysiology of diabetic gastroparesis with a focus on oxidative damage and how activation and polarization of different subtypes of macrophages in the muscularis propria determines development of delay in gastric emptying or protects against its development.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/nmo.12418

Cites

10 of 10 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In diabetes, insulin and IGF-1 deficiency causes muscle atrophy and reduced SCF production, leading to ICC depletion and impaired neuromuscular transmission.

    “In diabetes, insulin and IGF-1 deficiency causes muscle atrophy and reduced SCF production, leading to ICC depletion and impaired neuromuscular transmission [52–60].”

    From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [60]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 103

  1. [1]Hasler WL Wilson LA Parkman HP Koch KL Abell TL Nguyen L Pasricha PJ Snape WJ Factors related to abdominal pain in gastroparesis: contrast to patients with predominant nausea and vomiting Neurogastroenterol Motil 2013 25 427 438 e300 e301 23414452 PMC3907086
  2. [2]Parkman HP Camilleri M Farrugia G McCallum RW Bharucha AE Mayer EA Tack JF Spiller R Gastroparesis and functional dyspepsia: excerpts from the AGA/ANMS meeting Neurogastroenterol Motil 2010 22 113 133 20003077 PMC2892213
  3. [3]Parkman HP Yates K Hasler WL Nguyen L Pasricha PJ Snape WJ Farrugia G Koch KL Similarities and differences between diabetic and idiopathic gastroparesis Clin Gastroenterol Hepatol 2011 9 1056 1064 quiz e133-4. 21871247 PMC3499102
  4. [4]Camilleri M Grover M Farrugia G What are the important subsets of gastroparesis? Neurogastroenterol Motil 2012 24 597 603 22626059 PMC3785986
  5. [5]Nusrat S Bielefeldt K Gastroparesis on the rise: incidence vs awareness? Neurogastroenterol Motil 2013 25 16 22 22937956
  6. [6]Bharucha AE Camilleri M Forstrom LA Zinsmeister AR Relationship between clinical features and gastric emptying disturbances in diabetes mellitus Clin Endocrinol (Oxf) 2009 70 415 420 18727706 PMC3899345
  7. [7]Samsom M Vermeijden JR Smout AJ Van Doorn E Roelofs J Van Dam PS Martens EP Eelkman-Rooda SJ Prevalence of delayed gastric emptying in diabetic patients and relationship to dyspeptic symptoms: a prospective study in unselected diabetic patients Diabetes Care 2003 26 3116 3122 14578248
  8. [8]Jones KL Russo A Stevens JE Wishart JM Berry MK Horowitz M Predictors of delayed gastric emptying in diabetes Diabetes Care 2001 24 1264 1269 11423513
  9. [9]Horowitz M Maddox A Wishart J Harding P Chatterton B Shearman DC Relationships between oesophageal transit and solid and liquid gastric emptying in diabetes mellitus Eur J Nucl Med 1991 18 229 234 2070801
  10. [10]Janssen P Harris MS Jones M Masaoka T Farre R Tornblom H Van Oudenhove L Simren M The relation between symptom improvement and gastric emptying in the treatment of diabetic and idiopathic gastroparesis Am J Gastroenterol 2013 108 1382 1391 24005344
  11. [11]Lelic D Brock C Simren M Frokjaer JB Softeland E Dimcevski G Gregersen H Drewes AM The brain networks encoding visceral sensation in patients with gastrointestinal symptoms due to diabetic neuropathy Neurogastroenterol Motil 2014 26 46 58 24050116
  12. [13]Ordog T Hayashi Y Gibbons SJ Cellular pathogenesis of diabetic gastroenteropathy Minerva Gastroenterol Dietol 2009 55 315 343 19829287 PMC2854169
  13. [14]Aylett P Gastric emptying and change of blood glucose level, as affected by glucagon and insulin Clin Sci 1962 22 171 178 13863498
  14. [15]Barnett JL Chung OY Serum Glucose-Concentration as a Modulator of Interdigestive Gastric-Motility Gastroenterology 1988 94 739 744 3338642
  15. [16]Grabauskas G Song I Zhou S Owyang C Electrophysiological identification of glucose-sensing neurons in rat nodose ganglia J Physiol 2010 588 617 632 20008464 PMC2828136
  16. [17]Babic T Troy AE Fortna SR Browning KN Glucose-dependent trafficking of 5-HT3 receptors in rat gastrointestinal vagal afferent neurons Neurogastroenterol Motil 2012 24 e476 e488 22845622 PMC3440531
  17. [18]Grover M Farrugia G Lurken MS Bernard CE Faussone-Pellegrini MS Smyrk TC Parkman HP Abell TL Cellular changes in diabetic and idiopathic gastroparesis Gastroenterology 2011 140 1575 1585 e8 21300066 PMC3081914
  18. [19]Vittal H Farrugia G Gomez G Pasricha PJ Mechanisms of disease: the pathological basis of gastroparesis--a review of experimental and clinical studies Nat Clin Pract Gastroenterol Hepatol 2007 4 336 346 17541447
  19. [20]Choi KM Gibbons SJ Nguyen TV Stoltz GJ Lurken MS Ordog T Szurszewski JH Farrugia G Heme oxygenase-1 protects interstitial cells of Cajal from oxidative stress and reverses diabetic gastroparesis Gastroenterology 2008 135 2055 2064 64 e1 64 e2 18926825 PMC2796242
  20. [21]Choi KM Kashyap PC Dutta N Stoltz GJ Ordog T Shea Donohue T Bauer AJ Linden DR CD206-positive M2 macrophages that express heme oxygenase-1 protect against diabetic gastroparesis in mice Gastroenterology 2010 138 2399 409 409 e1 20178793 PMC2883675
  21. [22]Kashyap PC Choi KM Dutta N Linden DR Szurszewski JH Gibbons SJ Farrugia G Carbon monoxide reverses diabetic gastroparesis in NOD mice Am J Physiol Gastrointest Liver Physiol 2010 298 G1013 G1019 20378827 PMC3284279
  22. [23]Yagihashi S Sima AA Diabetic autonomic neuropathy in BB rat. Ultrastructural and morphometric changes in parasympathetic nerves Diabetes 1986 35 733 743 3721060
  23. [24]Kniel PC Junker U Perrin IV Bestetti GE Rossi GL Varied effects of experimental diabetes on the autonomic nervous system of the rat Lab Invest 1986 54 523 530 3702343
  24. [25]Duchen LW Anjorin A Watkins PJ Mackay JD Pathology of autonomic neuropathy in diabetes mellitus Ann Intern Med 1980 92 301 303 6243893
  25. [27]Faussone-Pellegrini MS Grover M Pasricha PJ Bernard CE Lurken MS Smyrk TC Parkman HP Abell TL Ultrastructural differences between diabetic and idiopathic gastroparesis J Cell Mol Med 2012 16 1573 1581 21914127 PMC3250562
  26. [28]Grover M Bernard CE Pasricha PJ Lurken MS Faussone-Pellegrini MS Smyrk TC Parkman HP Abell TL Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium Neurogastroenterol Motil 2012 24 531 539 e249 22339929 PMC3353102
  27. [29]Takahashi T Nakamura K Itoh H Sima AA Owyang C Impaired expression of nitric oxide synthase in the gastric myenteric plexus of spontaneously diabetic rats Gastroenterology 1997 113 1535 1544 9352855
  28. [30]Zandecki M Vanden Berghe P Depoortere I Geboes K Peeters T Janssens J Tack J Characterization of myenteric neuropathy in the jejunum of spontaneously diabetic BB-rats Neurogastroenterol Motil 2008 20 818 828 18312542
  29. [31]Jeyabal PV Kumar R Gangula PR Micci MA Pasricha PJ Inhibitors of advanced glycation end-products prevent loss of enteric neuronal nitric oxide synthase in diabetic rats Neurogastroenterol Motil 2008 20 253 261 17971026
  30. [32]Lies B Groneberg D Friebe A Toward a better understanding of gastrointestinal nitrergic neuromuscular transmission Neurogastroenterol Motil 2014 26 901 912 24827638
  31. [33]Watkins CC Sawa A Jaffrey S Blackshaw S Barrow RK Snyder SH Ferris CD Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy J Clin Invest 2000 106 373 384 10930440 PMC314323
  32. [34]Pasricha PJ Pehlivanov ND Gomez G Vittal H Lurken MS Farrugia G Changes in the gastric enteric nervous system and muscle: a case report on two patients with diabetic gastroparesis BMC Gastroenterol 2008 8 21 18513423 PMC2442096
  33. [35]Rivera LR Poole DP Thacker M Furness JB The involvement of nitric oxide synthase neurons in enteric neuropathies Neurogastroenterol Motil 2011 23 980 988 21895878
  34. [36]Korenaga K Micci MA Taglialatela G Pasricha PJ Suppression of nNOS expression in rat enteric neurones by the receptor for advanced glycation end-products Neurogastroenterol Motil 2006 18 392 400 16629867
  35. [37]Gangula PR Maner WL Micci MA Garfield RE Pasricha PJ Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum Am J Physiol Gastrointest Liver Physiol 2007 292 G725 G733 17347455 PMC2786258
  36. [38]Gangula PR Mukhopadhyay S Pasricha PJ Ravella K Sepiapterin reverses the changes in gastric nNOS dimerization and function in diabetic gastroparesis Neurogastroenterol Motil 2010 22 1325 1331 e351 e352 20731778 PMC3072796
  37. [39]Gangula PR Mukhopadhyay S Ravella K Cai S Channon KM Garfield RE Pasricha PJ Tetrahydrobiopterin (BH4), a cofactor for nNOS, restores gastric emptying and nNOS expression in female diabetic rats Am J Physiol Gastrointest Liver Physiol 2010 298 G692 G699 20185690 PMC2867432
  38. [40]Farrugia G Interstitial cells of Cajal in health and disease Neurogastroenterol Motil 2008 20 Suppl 1 54 63 18402642
  39. [41]Angeli TR O'Grady G Du P Paskaranandavadivel N Pullan AJ Bissett IP Cheng LK Circumferential and functional re-entry of in vivo slow-wave activity in the porcine small intestine Neurogastroenterol Motil 2013 25 e304 e314 23489929 PMC3781238
  40. [42]O'Grady G Du P Paskaranandavadivel N Angeli TR Lammers WJ Asirvatham SJ Windsor JA Farrugia G Rapid high-amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias Neurogastroenterol Motil 2012 24 e299 e312 22709238 PMC3383091
  41. [43]Lammers WJ Arrhythmias in the gut Neurogastroenterol Motil 2013 25 353 357 23490042
  42. [44]O'Grady G Angeli TR Du P Lahr C Lammers WJ Windsor JA Abell TL Farrugia G Abnormal initiation and conduction of slow-wave activity in gastroparesis, defined by high-resolution electrical mapping Gastroenterology 2012 143 589 598 e1 e3 22643349 PMC3429650
  43. [45]Burns AJ Lomax AE Torihashi S Sanders KM Ward SM Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach Proc Natl Acad Sci U S A 1996 93 12008 12013 8876253 PMC38174
  44. [46]Ward SM Beckett EA Wang X Baker F Khoyi M Sanders KM Interstitial cells of Cajal mediate cholinergic neurotransmission from enteric motor neurons J Neurosci 2000 20 1393 1403 10662830 PMC6772355
  45. [47]Klein S Seidler B Kettenberger A Sibaev A Rohn M Feil R Allescher HD Vanderwinden JM Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity Nat Commun 2013 4 1630 23535651
  46. [48]Iwasaki H Kajimura M Osawa S Kanaoka S Furuta T Ikuma M Hishida A A deficiency of gastric interstitial cells of Cajal accompanied by decreased expression of neuronal nitric oxide synthase and substance P in patients with type 2 diabetes mellitus J Gastroenterol 2006 41 1076 1087 17160518
  47. [49]Lin Z Sarosiek I Forster J Damjanov I Hou Q McCallum RW Association of the status of interstitial cells of Cajal and electrogastrogram parameters, gastric emptying and symptoms in patients with gastroparesis Neurogastroenterol Motil 2010 22 56 61 e10 19614868
  48. [50]Ordog T Takayama I Cheung WK Ward SM Sanders KM Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis Diabetes 2000 49 1731 1739 11016458
  49. [51]He CL Soffer EE Ferris CD Walsh RM Szurszewski JH Farrugia G Loss of interstitial cells of cajal and inhibitory innervation in insulin-dependent diabetes Gastroenterology 2001 121 427 434 11487552
  50. [52]Wang XY Huizinga JD Diamond J Liu LW Loss of intramuscular and submuscular interstitial cells of Cajal and associated enteric nerves is related to decreased gastric emptying in streptozotocin-induced diabetes Neurogastroenterol Motil 2009 21 1095-e92 19566589
  51. [53]Choi KM Zhu J Stoltz GJ Vernino S Camilleri M Szurszewski JH Gibbons SJ Farrugia G Determination of gastric emptying in nonobese diabetic mice Am J Physiol Gastrointest Liver Physiol 2007 293 G1039 G1045 17884976
  52. [54]Horvath VJ Vittal H Lorincz A Chen H Almeida-Porada G Redelman D Ordog T Reduced stem cell factor links smooth myopathy and loss of interstitial cells of cajal in murine diabetic gastroparesis Gastroenterology 2006 130 759 770 16530517
  53. [55]Brownlee M Biochemistry and molecular cell biology of diabetic complications Nature 2001 414 813 820 11742414
  54. [56]Vincent AM Callaghan BC Smith AL Feldman EL Diabetic neuropathy: cellular mechanisms as therapeutic targets Nat Rev Neurol 2011 7 573 583 21912405
  55. [57]Vincent AM Perrone L Sullivan KA Backus C Sastry AM Lastoskie C Feldman EL Receptor for advanced glycation end products activation injures primary sensory neurons via oxidative stress Endocrinology 2007 148 548 558 17095586
  56. [58]Drel VR Pacher P Stevens MJ Obrosova IG Aldose reductase inhibition counteracts nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic rat kidney and high-glucose-exposed human mesangial cells Free Radic Biol Med 2006 40 1454 1465 16631535 PMC2225484
  57. [60]Ravella K Yang H Gangula PR Impairment of gastric nitrergic and NRF2 system in apolipoprotein E knockout mice Dig Dis Sci 2012 57 1504 1509 22302246 PMC3677538
  58. [61]Chandrasekharan B Anitha M Blatt R Shahnavaz N Kooby D Staley C Mwangi S Jones DP Colonic motor dysfunction in human diabetes is associated with enteric neuronal loss and increased oxidative stress Neurogastroenterol Motil 2011 23 131 138 e26 20939847 PMC3020997
  59. [62]Cosyns SM Dhaese I Thoonen R Buys ES Vral A Brouckaert P Lefebvre RA Heme deficiency of soluble guanylate cyclase induces gastroparesis Neurogastroenterol Motil 2013 25 e339 e352 23551931 PMC4932850
  60. [63]Nezami BG Mwangi SM Lee JE Jeppsson S Anitha M Yarandi SS Farris AB 3rd Srinivasan S MicroRNA 375 Mediates Palmitate-Induced Enteric Neuronal Damage and High-Fat Diet-Induced Delayed Intestinal Transit in Mice Gastroenterology 2014 146 473 483 e3 24507550 PMC3920196
  61. [64]Alcaraz MJ Fernandez P Guillen MI Anti-inflammatory actions of the heme oxygenase-1 pathway Curr Pharm Des 2003 9 2541 2551 14529552
  62. [65]Weis N Weigert A von Knethen A Brune B Heme oxygenase-1 contributes to an alternative macrophage activation profile induced by apoptotic cell supernatants Mol Biol Cell 2009 20 1280 1288 19129475 PMC2649271
  63. [66]Abraham NG Kappas A Pharmacological and clinical aspects of heme oxygenase Pharmacol Rev 2008 60 79 127 18323402
  64. [67]Shotton HR Lincoln J Diabetes only affects nitric oxide synthase-containing myenteric neurons that do not contain heme oxygenase 2 Brain Res 2006 1068 248 256 16375869
  65. [68]Mogami S Suzuki H Tsugawa H Fukuhara S Hibi T Impaired heme oxygenase-1 induction in the gastric antrum induces disruption of the interstitial cells of Cajal network in a rat model of streptozotocin-induced diabetes Neurogastroenterol Motil 2013 25 609-e465 23534481
  66. [69]Murray PJ Wynn TA Protective and pathogenic functions of macrophage subsets Nat Rev Immunol 2011 11 723 737 21997792 PMC3422549
  67. [70]Smith PD Smythies LE Shen R Greenwell-Wild T Gliozzi M Wahl SM Intestinal macrophages and response to microbial encroachment Mucosal Immunol 2011 4 31 42 20962772 PMC3821935
  68. [71]Denning TL Wang YC Patel SR Williams IR Pulendran B Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses Nat Immunol 2007 8 1086 1094 17873879
  69. [72]Mikkelsen HB Macrophages in the external muscle layers of mammalian intestines Histol Histopathol 1995 10 719 36 7579823
  70. [73]Mikkelsen HB Rumessen JJ Characterization of macrophage-like cells in the external layers of human small and large intestine Cell Tissue Res 1992 270 273 279 1451172
  71. [74]Mikkelsen HB Thuneberg L Rumessen JJ Thorball N Macrophage-like cells in the muscularis externa of mouse small intestine Anat Rec 1985 213 77 86 2416252
  72. [75]Mikkelsen HB Garbarsch C Tranum-Jensen J Thuneberg L Macrophages in the small intestinal muscularis externa of embryos, newborn and adult germ-free mice J Mol Histol 2004 35 377 387 15503811
  73. [76]Rumessen JJ Vanderwinden JM Rasmussen H Hansen A Horn T Ultrastructure of interstitial cells of Cajal in myenteric plexus of human colon Cell Tissue Res 2009 337 197 212 19506909
  74. [77]Mikkelsen HB Interstitial cells of Cajal, macrophages and mast cells in the gut musculature: morphology, distribution, spatial and possible functional interactions J Cell Mol Med 2010 14 818 832 20132411 PMC3823114
  75. [78]Phillips RJ Powley TL Macrophages associated with the intrinsic and extrinsic autonomic innervation of the rat gastrointestinal tract Auton Neurosci 2012 169 12 27 22436622 PMC3361649
  76. [79]Bauer AJ Boeckxstaens GE Mechanisms of postoperative ileus Neurogastroenterol Motil 2004 16 54 60 15357852
  77. [80]Martinez FO Gordon S The M1 and M2 paradigm of macrophage activation: time for reassessment F1000Prime Rep 2014 6 13 24669294 PMC3944738
  78. [81]Stout RD Suttles J Immunosenescence and macrophage functional plasticity: dysregulation of macrophage function by age-associated microenvironmental changes Immunol Rev 2005 205 60 71 15882345 PMC1201508
  79. [83]Toshchakov V Jones B Perera P-Y Thomas K Cody M Zhang S Williams B Major J TLR4, but not TLR2, mediates IFN-beta-induced STAT1alpha/beta-dependent gene expression in macrophages Nature Immunol 2002 3 392 398 11896392
  80. [85]Ricote M Li A Willson T Kelly C Glass C The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation Nature 1998 391 79 82 9422508
  81. [86]Takeda K Tanaka T Shi W Matsumoto M Minami M Kashiwamura S Nakanishi K Yoshida N Essential role of Stat6 in IL-4 signalling Nature 1996 380 627 630 8602263
  82. [88]Bonizzi G Karin M The two NF-kappaB activation pathways and their role in innate and adaptive immunity Trends Immunol 2004 25 280 288 15145317
  83. [89]Sica A Bronte V Altered macrophage differentiation and immune dysfunction in tumor development J Clin Invest 2007 117 1155 1166 17476345 PMC1857267
  84. [90]Ivashkiv LB Epigenetic regulation of macrophage polarization and function Trends Immunol 2013 34 216 223 23218730 PMC3647003
  85. [91]Martinez FO Sica A Mantovani A Locati M Macrophage activation and polarization Front Biosci 2008 13 453 461 17981560
  86. [92]Mosser D Edwards J Exploring the full spectrum of macrophage activation Nature Rev Immunol 2008 8 958 969 19029990 PMC2724991
  87. [93]Nathan C Ding A Nonresolving inflammation Cell 2010 140 871 882 20303877
  88. [95]Gong P Stewart D Hu B Li N Cook J Nel A Alam J Activation of the mouse heme oxygenase-1 gene by 15-deoxy-Delta(12,14)-prostaglandin J(2) is mediated by the stress response elements and transcription factor Nrf2 Antioxid Redox Signal 2002 4 249 257 12006176
  89. [96]Anthony RM Urban JF Jr Alem F Hamed HA Rozo CT Boucher JL Van Rooijen N Gause WC Memory T(H)2 cells induce alternatively activated macrophages to mediate protection against nematode parasites Nat Med 2006 12 955 960 16892038 PMC1955764
  90. [97]Gordon S Martinez FO Alternative activation of macrophages: mechanism and functions Immunity 2010 32 593 604 20510870
  91. [98]Stein M Keshav S Harris N Gordon S Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation J Exp Med 1992 176 287 292 1613462 PMC2119288
  92. [99]Jenkins SJ Ruckerl D Cook PC Jones LH Finkelman FD van Rooijen N MacDonald AS Allen JE Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation Science 2011 332 1284 1288 21566158 PMC3128495
  93. [100]Munder M Eichmann K Modolell M Alternative Metabolic States in Murine Macrophages Reflected by the Nitric Oxide Synthase/Arginase Balance: Competitive Regulation by CD4+ T Cells Correlates with Th1/Th2 Phenotype J Immunol 1998 160 5347 5354 9605134
  94. [101]Hesse M Modolell M La Flamme A Schito M Fuentes J Cheever A Pearce E Wynn T Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism J Immunol 2001 167 6533 6544 11714822
  95. [103]Schneemann M Schoeden G Macrophage biology and immunology: man is not a mouse J Leukoc Biol 2007 81 579 discussion 89. 29350850
  96. [104]Recalcati S Locati M Marini A Santambrogio P Zaninotto F De Pizzol M Zammataro L Girelli D Differential regulation of iron homeostasis during human macrophage polarized activation Eur J Immunol 2010 40 824 835 20039303
  97. [106]Matteoli G Boeckxstaens GE The vagal innervation of the gut and immune homeostasis Gut 2013 62 1214 1222 23023166 PMC3711371
  98. [109]Bernard CE Gibbons SJ Mann IS Froschauer L Parkman HP Harbison S Abell TL Snape WJ Association of low numbers of CD206-positive cells with loss of ICC in the gastric body of patients with diabetic gastroparesis Neurogastroenterol Motil 2014 (in press). PMC4149814 25041465
  99. [110]Hamann J Koning N Pouwels W Ulfman LH van Eijk M Stacey M Lin HH Gordon S EMR1, the human homolog of F4/80, is an eosinophil-specific receptor Eur J Immunol 2007 37 2797 2802 17823986
  100. [111]Raes G Brys L Dahal BK Brandt J Grooten J Brombacher F Vanham G Noël W Macrophage galactose-type C-type lectins as novel markers for alternatively activated macrophages elicited by parasitic infections and allergic airway inflammation J Leukoc Biol 2005 77 321 327 15591125
  101. [112]Martinez FO Helming L Milde R Varin A Melgert BN Draijer C Thomas B Fabbri M Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences Blood 2013 121 e57 e69 23293084
  102. [113]Mehta K Kumar A Kim HI Transglutaminase 2: a multi-tasking protein in the complex circuitry of inflammation and cancer Biochem Pharmacol 2010 80 1921 1929 20599779
  103. [114]Motterlini R Otterbein LE The therapeutic potential of carbon monoxide Nat Rev Drug Discov 2010 9 728 743 20811383

Cited by

Sorted by citations

Authors
Neshatian, L., Gibbons, S. J., & Farrugia, G.
Affiliations
Mayo Clinic (US)
Corresponding author
Farrugia, G.
ORCID
Venue
Neurogastroenterology & Motility
Publisher
Wiley
Published
2014-08-28
Volume
27
Issue
1
Pages
7-18
ISSN
  • 1350-1925 (ISSN-L)
  • 1365-2982
DOI
10.1111/nmo.12418
PMC
PMC4409126
OpenAlex
W1974169016
Cited by
55
References
10
Citations by year
2026: 3 · 2025: 6 · 2024: 5 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 7 · 2015: 1 · 2014: 1
FWCI
0.76
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Neurogastroenterology & Motility (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (DK57061, DK68055, DK74008, DK76169)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
  • Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
Keywords
diabetic gastroparesis, macrophages, heme oxygenase-1, oxidative stress, macrophage polarization, delayed gastric emptying, muscularis propria, interstitial cells of Cajal, diabetic neuropathy, macrophage-targeted therapy
MeSH terms
Animals, Diabetic Neuropathies, Heme Oxygenase (Decyclizing), Humans, Macrophages, Oxidative Stress, Gastroparesis, Gastrointestinal Tract, Diabetes Complications, Mice, Rats, Interstitial Cells of Cajal

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review