Distinct stimulus-dependent neutrophil dynamics revealed by real-time imaging of intestinal mucosa after acute injury

  1. Azcutia, Veronica 1
  2. Kelm, Matthias 1
  3. Kim, Seonyoung 4
  4. Luissint, Anny-Claude 1
  5. Flemming, Sven 1
  6. Abernathy-Close, Lisa 2
  7. Young, Vincent B 23
  8. Nusrat, Asma 1
  9. Miller, Mark J 4
  10. Parkos, Charles A 1
  1. 1 Department of Pathology, University of Michigan ; Ann Arbor, MI 48109 , USA
  2. 2 Department of Internal Medicine/Division of Infectious Diseases, University of Michigan ; Ann Arbor, MI 48109 , USA
  3. 3 Department of Microbiology and Immunology, University of Michigan ; Ann Arbor, MI 48109 , USA
  4. 4 Department of Internal Medicine, Washington University School of Medicine ; Saint Louis, MO 63110 , USA
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Revista:
PNAS Nexus

ISSN: 2752-6542

Año de publicación: 2022

Volumen: 1

Número: 5

Páginas: 1-13

Tipo: Artículo

DOI: 10.1093/PNASNEXUS/PGAC249 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: PNAS Nexus

Resumen

Clinical symptoms in many inflammatory diseases of the intestine are directly related to neutrophil (PMN) migration across colonic mucosa and into the intestinal lumen, yet in-vivo studies detailing this process are lacking. Using real-time intravital microscopy and a new distal colon loop model, we report distinct PMN migratory dynamics in response to several models of acute colonic injury. PMNs exhibited rapid swarming responses after mechanically induced intestinal wounds. Similar numbers of PMNs infiltrated colonic mucosa after wounding in germ-free mice, suggesting microbiota-independent mechanisms. By contrast, acute mucosal injury secondary to either a treatment of mice with dextran sodium sulfate or an IL-10 receptor blockade model of colitis resulted in lamina propria infiltration with PMNs that were largely immotile. Biopsy wounding of colonic mucosa in DSS-treated mice did not result in enhanced PMN swarming however, intraluminal application of the neutrophil chemoattractant LTB4 under such conditions resulted in enhanced transepithelial migration of PMNs. Analyses of PMNs that had migrated into the colonic lumen revealed that the majority of PMNs were directly recruited from the circulation and not from the immotile pool in the mucosa. Decreased PMN motility parallels upregulation of the receptor CXCR4 and apoptosis. Similarly, increased expression of CXCR4 on human PMNs was observed in colonic biopsies from people with active ulcerative colitis. This new approach adds an important tool to investigate mechanisms regulating PMN migration across mucosa within the distal intestine and will provide new insights for developing future anti-inflammatory and pro-repair therapies.

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Referencias bibliográficas

  • Mayadas, (2014), Annu Rev Pathol, 9, pp. 181, 10.1146/annurev-pathol-020712-164023
  • Peiseler, (2019), J Clin Invest, 129, pp. 2629, 10.1172/JCI124616
  • Wang, (2018), Cell Tissue Res, 371, pp. 531, 10.1007/s00441-017-2785-7
  • Kolaczkowska, (2013), Nat Rev Immunol, 13, pp. 159, 10.1038/nri3399
  • Fournier, (2012), Mucosal Immunol, 5, pp. 354, 10.1038/mi.2012.24
  • Parkos, (2016), Am J Pathol, 186, pp. 1404, 10.1016/j.ajpath.2016.02.001
  • Brazil, (2016), Immunol Rev, 273, pp. 94, 10.1111/imr.12446
  • Ley, (2007), Nat Rev Immunol, 7, pp. 678, 10.1038/nri2156
  • Leick, (2014), Cell Tissue Res, 355, pp. 647, 10.1007/s00441-014-1809-9
  • Kobayashi, (2017), Front Cell Infect Microbiol, 7, pp. 159, 10.3389/fcimb.2017.00159
  • Pillay, (2010), Blood, 116, pp. 625, 10.1182/blood-2010-01-259028
  • Boerner, (2021), J Vis Exp, 11, pp. e62093
  • Flemming, (2018), JCI insight, 3, pp. e99722, 10.1172/jci.insight.99722
  • Sumagin, (2014), Mucosal Immunol, 7, pp. 905, 10.1038/mi.2013.106
  • Azcutia, (2021), Mucosal Immunol, 14, pp. 331, 10.1038/s41385-020-0316-4
  • Brazil, (2013), J Immunol, 191, pp. 4804, 10.4049/jimmunol.1301307
  • Chtanova, (2008), Immunity, 29, pp. 487, 10.1016/j.immuni.2008.07.012
  • Kreisel, (2010), Proc Natl Acad Sci U S A, 107, pp. 18073, 10.1073/pnas.1008737107
  • Nishi, (2017), J Clin Invest, 127, pp. 3810, 10.1172/JCI94039
  • Kullberg, (1998), Infect Immun, 66, pp. 5157, 10.1128/IAI.66.11.5157-5166.1998
  • Kullberg, (2006), J Exp Med, 203, pp. 2485, 10.1084/jem.20061082
  • Reed, (2019), Nat Commun, 10, pp. 5004, 10.1038/s41467-019-12968-y
  • Parkos, (1996), J Cell Biol, 132, pp. 437, 10.1083/jcb.132.3.437
  • Martin, (2003), Immunity, 19, pp. 583, 10.1016/S1074-7613(03)00263-2
  • Wang, (2017), Science, 358, pp. 111, 10.1126/science.aam9690
  • Kim, (2006), Blood, 108, pp. 812, 10.1182/blood-2005-10-4162
  • Semerad, (2005), Blood, 106, pp. 3020, 10.1182/blood-2004-01-0272
  • Faust, (2000), Blood, 96, pp. 719, 10.1182/blood.V96.2.719
  • Yam, (2020), Cell Immunol, 350, pp. 103898, 10.1016/j.cellimm.2019.01.003
  • Lammermann, (2013), Nature, 498, pp. 371, 10.1038/nature12175
  • Ng, (2011), J Invest Dermatol, 131, pp. 2058, 10.1038/jid.2011.179
  • Borregaard, (2007), Trends Immunol, 28, pp. 340, 10.1016/j.it.2007.06.002
  • Lammermann, (2019), Immunol Rev, 289, pp. 205, 10.1111/imr.12752
  • Pitcher, (1998), Annu Rev Biochem, 67, pp. 653, 10.1146/annurev.biochem.67.1.653
  • Steury, (2017), Adv Immunol, 136, pp. 227, 10.1016/bs.ai.2017.05.003
  • Freedman, (1996), Recent Prog Horm Res, 51, pp. 319
  • Devi, (2013), J Exp Med, 210, pp. 2321, 10.1084/jem.20130056
  • Isles, (2019), Front Immunol, 10, pp. 1784, 10.3389/fimmu.2019.01784
  • Casanova-Acebes, (2018), J Exp Med, 215, pp. 2778, 10.1084/jem.20181468
  • de Oliveira, (2016), Nat Rev Immunol, 16, pp. 378, 10.1038/nri.2016.49
  • Uhl, (2016), Blood, 128, pp. 2327, 10.1182/blood-2016-05-718999
  • Deniset, (2018), J Leukocyte Biol, 103, pp. 829, 10.1002/JLB.3RI0917-361R
  • Rosales, (2018), Front Physiol, 9, pp. 113, 10.3389/fphys.2018.00113
  • Grieshaber-Bouyer, (2021), Nat Commun, 12, pp. 2856, 10.1038/s41467-021-22973-9
  • De Filippo, (2018), Eur J Clin Invest, 48 Suppl 2, pp. e12949, 10.1111/eci.12949
  • Whyte, (1993), J Immunol, 150, pp. 5124, 10.4049/jimmunol.150.11.5124
  • Zhang, (2015), Nature, 525, pp. 528, 10.1038/nature15367
  • Phillipson, (2019), Trends Immunol, 40, pp. 635, 10.1016/j.it.2019.05.001
  • Brazil, (2019), J Clin Invest, 129, pp. 2983, 10.1172/JCI124618
  • Neurath, (2012), Gut, 61, pp. 1619, 10.1136/gutjnl-2012-302830
  • Quiros, (2017), J Clin Invest, 127, pp. 3510, 10.1172/JCI90229
  • Krieglstein, (2002), J Clin Invest, 110, pp. 1773, 10.1172/JCI200215256
  • Medina-Contreras, (2016), J Immunol, 196, pp. 34, 10.4049/jimmunol.1501312
  • Wortel, (2021), ImmunoInformatics, 1–2, pp. 100003, 10.1016/j.immuno.2021.100003