title: Epithelial adhesion molecules and the regulation of intestinal homeostasis during neutrophil transepithelial migration.
abstract: Epithelial adhesion molecules play essential roles in regulating cellular function and maintaining mucosal tissue homeostasis. Some form epithelial junctional complexes to provide structural support for epithelial monolayers and act as a selectively permeable barrier separating luminal contents from the surrounding tissue. Others serve as docking structures for invading viruses and bacteria, while also regulating the immune response. They can either obstruct or serve as footholds for the immune cells recruited to mucosal surfaces. Currently, it is well appreciated that adhesion molecules collectively serve as environmental cue sensors and trigger signaling events to regulate epithelial function through their association with the cell cytoskeleton and various intracellular adapter proteins. Immune cells, particularly neutrophils (PMN) during transepithelial migration (TEM), can modulate adhesion molecule expression, conformation, and distribution, significantly impacting epithelial function and tissue homeostasis. This review discusses the roles of key intestinal epithelial adhesion molecules in regulating PMN trafficking and outlines the potential consequences on epithelial function.
authors.affiliation: Department of Pathology and Laboratory Medicine; Epithelial Pathobiology and Mucosal Inflammation Unit; Emory University ; Atlanta, GA USA.
authors.forename: Ronen
authors.initials: R
authors.lastname: Sumagin
authors.affiliation: Department of Pathology and Laboratory Medicine; Epithelial Pathobiology and Mucosal Inflammation Unit; Emory University ; Atlanta, GA USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Parkos
keywords: AJs, adherens junctions; CAR, coxsackie and adenovirus receptor; CLMP, CAR-like protein; CTLs, cytotoxic T lymphocytes; CTX, thymocyte Xenopus; DMs, Desmosomes; Dsc-2, desmocollin-2; Dsg-2, desmoglein-2; E-cadherin, epithelial cadherin; EGFR, Epithelial growth factor receptor; EMT, epithelial-mesenchymal transition; EpCAM, epithelial cell adhesion molecule; IBD, inflammatory bowel diseases; ICAM-1, intercellular adhesion molecule-1; IECs, intestinal epithelial cells; JAM, junctional adhesion molecules; LAD, leukocyte adhesion deficiency; LTB-4, lipid leukotriene B4; MIP1 α, macrophage inflammatory protein 1 alpha; MLCK, myosin light chain kinase; MMPs, matrix metalloproteases; NF-κB, nuclear factor kappa B; NO, nitric oxide; PARS, protease-activated receptors; PI3K, phosphatidylinositol 3-kinase; PMN, polymorphonuclear cells; SGD, specific granule deficiency; SIRPa, signal regulatory protein alpha; TEM, transepithelial migration; TGF-β, transforming growth factor beta; TIAM1, metastasis-inducing protein 1; TJs, tight junctions; TSP-1, thrombospondin-1; adhesion molecules; barrier; cell migration; epithelial cells; neutrophils; sLea, sialyl Lewis A
references.citation: Biochem Pharmacol. 2010 May 15;79(10):1496-505
references.pmid: 20096665
references.citation: Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15191-6
references.pmid: 11734628
references.citation: J Biol Chem. 2000 Feb 25;275(8):5773-8
references.pmid: 10681565
references.citation: J Exp Med. 2007 Mar 19;204(3):559-70
references.pmid: 17325197
references.citation: J Cell Biol. 1994 Jul;126(2):391-401
references.pmid: 7518464
references.citation: Pharmacol Rep. 2009 Jan-Feb;61(1):22-32
references.pmid: 19307690
references.citation: Genes Dev. 1999 Jan 1;13(1):35-48
references.pmid: 9887098
references.citation: PLoS One. 2012;7(9):e45499
references.pmid: 23029055
references.citation: Cancer Res. 2009 Jul 15;69(14 ):5627-9
references.pmid: 19584271
references.citation: J Pharmacol Exp Ther. 2006 Apr;317(1):309-16
references.pmid: 16371447
references.citation: J Immunol. 2010 May 1;184(9):5242-52
references.pmid: 20363969
references.citation: Clin Sci (Lond). 1991 Oct;81(4):477-81
references.pmid: 1682080
references.citation: J Exp Med. 1997 Dec 15;186(12):1985-96
references.pmid: 9396767
references.citation: Mol Med. 1996 Jul;2(4):489-505
references.pmid: 8827719
references.citation: Am J Physiol Gastrointest Liver Physiol. 2001 Sep;281(3):G705-17
references.pmid: 11518683
references.citation: J Exp Med. 2007 Dec 24;204(13):3067-76
references.pmid: 18039951
references.citation: J Immunol. 2006 Nov 1;177(9):6440-9
references.pmid: 17056576
references.citation: J Cell Sci. 1996 Sep;109 ( Pt 9):2287-98
references.pmid: 8886979
references.citation: J Clin Invest. 2010 Jun;120(6):1824-35
references.pmid: 20484816
references.citation: Inflamm Bowel Dis. 2005 Dec;11(12):1085-91
references.pmid: 16306771
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20262-7
references.pmid: 18077379
references.citation: Cold Spring Harb Perspect Biol. 2009 Aug;1(2):a002543
references.pmid: 20066089
references.citation: BMC Cell Biol. 2009 Dec 09;10:85
references.pmid: 20003227
references.citation: J Immunol. 1985 May;134(5):3307-15
references.pmid: 2984286
references.citation: J Biol Chem. 2002 Nov 22;277(47):44754-9
references.pmid: 12223485
references.citation: Crit Care Med. 2004 Jul;32(7):1460-9
references.pmid: 15241089
references.citation: J Immunol. 1994 Oct 1;153(7):3189-98
references.pmid: 7916369
references.citation: Am J Pathol. 2001 Dec;159(6):2001-9
references.pmid: 11733350
references.citation: J Biol Chem. 1995 May 5;270(18):10531-9
references.pmid: 7537733
references.citation: Mucosal Immunol. 2014 Jul;7(4):905-15
references.pmid: 24345805
references.citation: Exp Cell Res. 2006 May 15;312(9):1566-80
references.pmid: 16542650
references.citation: J Cell Biol. 1996 Aug;134(4):985-1001
references.pmid: 8769422
references.citation: FASEB J. 2005 Jun;19(8):950-9
references.pmid: 15923405
references.citation: J Cell Physiol. 1989 Aug;140(2):396-402
references.pmid: 2745570
references.citation: Blood. 1999 Dec 1;94(11):3633-43
references.pmid: 10572074
references.citation: Arterioscler Thromb Vasc Biol. 2009 Aug;29(8):1193-9
references.pmid: 19498176
references.citation: Physiol Rev. 2013 Apr;93(2):525-69
references.pmid: 23589827
references.citation: J Cell Biol. 1996 Feb;132(3):437-50
references.pmid: 8636220
references.citation: Nat Rev Mol Cell Biol. 2000 Dec;1(3):208-16
references.pmid: 11252896
references.citation: Eur J Immunol. 2003 May;33(5):1399-408
references.pmid: 12731067
references.citation: Mol Biol Cell. 2013 Sep;24(18):2849-60
references.pmid: 23885123
references.citation: Eur J Immunol. 1991 Oct;21(10):2415-21
references.pmid: 1680698
references.citation: Blood. 2005 Jul 15;106(2):584-92
references.pmid: 15811956
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Dec;285(6):L1305-11
references.pmid: 12909589
references.citation: Annu Rev Immunol. 1989;7:35-58
references.pmid: 2469439
references.citation: J Cell Biol. 2001 Nov 26;155(5):755-62
references.pmid: 11714729
references.citation: J Exp Med. 2003 Oct 6;198(7):999-1010
references.pmid: 14530374
references.citation: Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15990-5
references.pmid: 21880956
references.citation: Gastroenterology. 1997 Nov;113(5):1489-500
references.pmid: 9352851
references.citation: Arch Surg. 1996 Jan;131(1):24-9; discussion 29-30
references.pmid: 8546573
references.citation: J Immunol. 1999 Feb 15;162(4):2281-90
references.pmid: 9973505
references.citation: Thorax. 2009 Jan;64(1):81-8
references.pmid: 19103874
references.citation: Mol Biol Cell. 2007 Nov;18(11):4565-78
references.pmid: 17804817
references.citation: Dev Cell. 2010 Jan 19;18(1):52-63
references.pmid: 20152177
references.citation: Mol Biol Cell. 2009 Apr;20(7):1916-25
references.pmid: 19176753
references.citation: Mol Biol Cell. 2008 Nov;19(11):4687-93
references.pmid: 18768749
references.citation: Nat Clin Pract Gastroenterol Hepatol. 2005 Sep;2(9):416-22
references.pmid: 16265432
references.citation: Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10680-4
references.pmid: 7524101
references.citation: Am J Hum Genet. 1998 Dec;63(6):1588-93
references.pmid: 9837810
references.citation: Am J Respir Cell Mol Biol. 2002 Oct;27(4):446-54
references.pmid: 12356578
references.citation: Mucosal Immunol. 2014 Sep;7(5):1221-32
references.pmid: 24621992
references.citation: J Cell Biol. 1990 Dec;111(6 Pt 2):3129-39
references.pmid: 1980124
references.citation: Cell. 1996 Mar 22;84(6):923-32
references.pmid: 8601315
references.citation: J Immunol. 2010 Dec 1;185(11):7057-66
references.pmid: 21037096
references.citation: EMBO Rep. 2011 Apr;12(4):314-20
references.pmid: 21372850
references.citation: Exp Cell Res. 2005 Oct 15;310(1):140-51
references.pmid: 16112666
references.citation: Am J Physiol Gastrointest Liver Physiol. 2001 Jul;281(1):G216-28
references.pmid: 11408275
references.citation: Infect Immun. 1995 Oct;63(10):4054-62
references.pmid: 7558319
references.citation: Oncogene. 2004 Jul 29;23 (34):5748-58
references.pmid: 15195135
references.citation: Cancer Cell Int. 2003 Oct 14;3(1):17
references.pmid: 14613514
references.citation: Immunology. 1998 Feb;93(2):139-48
references.pmid: 9616361
references.citation: J Cell Biol. 1995 Sep;130(6):1473-82
references.pmid: 7559767
references.citation: J Biol Chem. 2004 Aug 27;279(35):37191-200
references.pmid: 15205458
references.citation: Nat Cell Biol. 2009 Feb;11(2):162-71
references.pmid: 19136966
references.citation: J Cell Biol. 2002 Nov 11;159(3):465-76
references.pmid: 12427869
references.citation: Cancer Metastasis Rev. 1999;18(1):15-30
references.pmid: 10505543
references.citation: J Immunol. 2004 Jan 15;172(2):1125-31
references.pmid: 14707087
references.citation: J Cell Biol. 1998 Jul 13;142(1):117-27
references.pmid: 9660867
references.citation: J Biol Chem. 2004 Apr 30;279(18):19230-8
references.pmid: 14985356
references.citation: Cell Adh Migr. 2011 Jul-Aug;5(4):306-14
references.pmid: 21715983
references.citation: Blood. 2013 Aug 1;122(5):770-80
references.pmid: 23757732
references.citation: J Cell Sci. 2013 Jan 15;126(Pt 2):554-64
references.pmid: 23203797
references.citation: J Immunol. 1994 Jun 15;152(12):5653-9
references.pmid: 8207198
references.citation: Breast Cancer Res. 2011 Mar 23;13(2):R31
references.pmid: 21429211
references.citation: J Immunol. 2013 Nov 1;191(9):4804-17
references.pmid: 24068663
references.citation: J Immunol. 2010 Dec 1;185(11):7026-36
references.pmid: 20974992
references.citation: Genes Dev. 2000 Jan 15;14(2):163-76
references.pmid: 10652271
references.citation: J Immunol. 1999 Jun 15;162(12):7285-93
references.pmid: 10358177
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2977-82
references.pmid: 11830641
references.citation: Tissue Barriers. 2013 Jan 1;1(1):e22993
references.pmid: 24665372
references.citation: Allergy. 1997 May;52(5):521-31
references.pmid: 9201363
references.citation: Oncogene. 2012 Mar 29;31(13):1636-48
references.pmid: 21841821
references.citation: Am J Pathol. 2007 Aug;171(2):386-95
references.pmid: 17600130
references.citation: J Biol Chem. 2000 Sep 1;275(35):26967-75
references.pmid: 10871609
references.citation: Blood. 2009 Jun 11;113(24):6246-57
references.pmid: 19211506
references.citation: Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G774-83
references.pmid: 20224006
references.citation: Mol Med. 2011 Mar-Apr;17(3-4):293-307
references.pmid: 21046059
references.citation: Am J Pathol. 2009 Aug;175(2):580-91
references.pmid: 19590041
references.citation: Nature. 2011 Jun 15;474(7351):298-306
references.pmid: 21677746
references.citation: Biochem Biophys Res Commun. 1989 Apr 28;160(2):813-9
references.pmid: 2541713
references.citation: Microb Pathog. 2008 Apr;44(4):311-9
references.pmid: 18054197
references.citation: Biochim Biophys Acta. 2008 Mar;1778(3):572-87
references.pmid: 17854763
references.citation: Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H969-H977
references.pmid: 18641276
references.citation: Thromb Haemost. 2002 Apr;87(4):712-21
references.pmid: 12008956
references.citation: Gut. 2005 Mar;54(3):364-8
references.pmid: 15710984
references.citation: Cold Spring Harb Perspect Biol. 2009 Aug;1(2):a002584
references.pmid: 20066090
references.citation: Nature. 2007 Jul 26;448(7152):427-34
references.pmid: 17653185
references.citation: Nat Rev Mol Cell Biol. 2003 Mar;4(3):225-36
references.pmid: 12612641
references.citation: Curr Biol. 2002 Mar 5;12(5):379-82
references.pmid: 11882288
references.citation: Am J Physiol Heart Circ Physiol. 2007 Nov;293(5):H2786-98
references.pmid: 17704289
references.citation: J Exp Med. 1995 Feb 1;181(2):669-75
references.pmid: 7530761
references.citation: J Cell Sci. 2000 Jul;113 ( Pt 13):2363-74
references.pmid: 10852816
references.citation: Sci Rep. 2013 Oct 07;3:2889
references.pmid: 24096322
references.citation: Nat Rev Immunol. 2007 Sep;7(9):678-89
references.pmid: 17717539
references.citation: Eur J Immunol. 2012 Dec;42(12):3369-80
references.pmid: 23001948
references.citation: EMBO J. 2001 Aug 15;20(16):4391-8
references.pmid: 11500366
references.citation: Nat Rev Mol Cell Biol. 2003 Jan;4(1):33-45
references.pmid: 12511867
references.citation: Mol Biol Cell. 2014 May;25(10):1574-85
references.pmid: 24672055
references.citation: Science. 2010 Sep 3;329(5996):1205-10
references.pmid: 20813954
references.citation: J Exp Med. 2006 Nov 27;203(12):2569-75
references.pmid: 17116736
references.citation: Nat Rev Mol Cell Biol. 2010 May;11(5):366-78
references.pmid: 20414258
references.citation: Proc Soc Exp Biol Med. 1997 Apr;214(4):318-27
references.pmid: 9111522
references.citation: J Immunol. 2008 Oct 15;181(8):5702-10
references.pmid: 18832729
references.citation: Am J Physiol. 1992 Jul;263(1 Pt 1):L79-87
references.pmid: 1353306
references.citation: Proc Natl Acad Sci U S A. 1988 Oct;85(20):7734-8
references.pmid: 2971974
references.citation: Oncotarget. 2013 Dec;4(12):2512-22
references.pmid: 24318272
references.citation: Apoptosis. 2002 Dec;7(6):493-8
references.pmid: 12370491
references.citation: J Biol Chem. 2000 Oct 6;275(40):30970-6
references.pmid: 10913139
references.citation: Biochem Biophys Res Commun. 2000 May 19;271(3):584-8
references.pmid: 10814505
references.citation: Cell Death Differ. 2003 Feb;10(2):153-62
references.pmid: 12700643
references.citation: J Cell Biol. 2005 Dec 19;171(6):939-45
references.pmid: 16365161
references.citation: J Biol Chem. 1999 Jan 8;274(2):559-62
references.pmid: 9872987
references.citation: J Clin Invest. 1991 Nov;88(5):1605-12
references.pmid: 1682344
references.citation: J Cell Biol. 1993 Oct;123(2):485-96
references.pmid: 7691831
references.citation: J Immunol. 1999 Nov 1;163(9):5029-38
references.pmid: 10528208
references.citation: J Immunol. 2002 Jul 1;169(1):476-86
references.pmid: 12077279
references.citation: Mol Cell Biol. 2003 Jun;23 (12 ):4267-82
references.pmid: 12773569
references.citation: Cell Motil Cytoskeleton. 1999;43(4):269-87
references.pmid: 10423269
references.citation: Mol Biol Cell. 2011 Apr 15;22(8):1121-34
references.pmid: 21325624
references.citation: Am J Physiol Cell Physiol. 2003 Nov;285(5):C1174-87
references.pmid: 12853285
references.citation: Int J Biochem Cell Biol. 2010 Jun;42(6):975-86
references.pmid: 20188849
references.citation: J Cell Sci. 2000 Mar;113 ( Pt 6):985-96
references.pmid: 10683147
references.citation: J Cell Sci. 2005 Oct 15;118(Pt 20):4901-12
references.pmid: 16219695
references.citation: Am J Physiol Gastrointest Liver Physiol. 2000 Nov;279(5):G851-7
references.pmid: 11052980
references.citation: Oncogene. 2014 Sep 4;33(36):4531-6
references.pmid: 24166502
references.citation: J Immunol. 2002 Nov 1;169(9):5270-8
references.pmid: 12391246
references.citation: J Exp Med. 1996 Oct 1;184(4):1213-23
references.pmid: 8879192
references.citation: Am J Pathol. 2009 Aug;175(2):571-9
references.pmid: 19608878
references.citation: Gastroenterology. 1999 Feb;116(2):301-9
references.pmid: 9922310
references.citation: J Surg Res. 2011 Nov;171(1):e1-7
references.pmid: 21872884
references.citation: Am J Pathol. 2008 Feb;172(2):521-33
references.pmid: 18187566
references.citation: Nat Med. 2011 Jan;17(1):96-104
references.pmid: 21151137
references.citation: Carcinogenesis. 2002 Dec;23(12):2119-22
references.pmid: 12507936