title: Leucocyte/endothelium interactions and microvessel permeability: coupled or uncoupled?
abstract: In response to infections or tissue injury, circulating leucocytes adhere to and migrate from the vessel lumen to interstitial inflammatory sites to combat invading pathogens. However, these defensive actions may also cause host tissue injury and microvascular dysfunction through oxidative bursts or enzyme release. For decades, the interaction between leucocytes and microvessel walls has been considered as a critical event leading to organ dysfunction. Extensive investigations have therefore focused on blocking specific adhesive ligands to prevent tissue injury. However, anti-adhesion therapies have shown limited success in preventing vascular dysfunction in clinical trials. Numerous studies have demonstrated temporal and spatial dissociations of leucocyte adhesion and/or emigration from permeability increases. The mechanisms that initiate the adhesion cascade have been found to be distinct from those that trigger the leucocyte oxidative burst responsible for increasing microvessel permeability. Recent studies demonstrated that endothelial activation by inflammatory mediators is critical for initiating platelet adhesion and platelet-dependent leucocyte recruitment resulting in augmented increases in microvessel permeability. These new developments suggest that targeting endothelial activation via directly enhancing endothelial barrier function might be a more efficient strategy than focusing on anti-adhesion or platelet/leucocyte depletion to prevent vascular damage during inflammation. Owing to space limitations and the wide range of studies in the field, this article will not serve as a comprehensive review. Instead, it will highlight the emerging evidence of adhesion-uncoupled permeability changes and establish a basis for re-evaluating the coupled relationship between leucocyte/platelet activation and microvessel permeability to achieve a better understanding of permeability regulation during inflammation.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV 26506-9229, USA. phe@hsc.wvu.edu
authors.forename: Pingnian
authors.initials: P
authors.lastname: He
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000276:immunology; D001826:Body Fluids / Q000378:metabolism*; D002199:Capillary Permeability; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000276:immunology*; D055806:Microvessels / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D009504:Neutrophils / Q000276:immunology; D010973:Platelet Adhesiveness; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018836:Inflammation Mediators; D017382:Reactive Oxygen Species
references.citation: Science. 1996 Jul 12;273(5272):252-5
references.pmid: 8662511
references.citation: Blood. 1996 Apr 15;87(8):3271-81
references.pmid: 8605343
references.citation: FASEB J. 2009 Apr;23(4):1011-22
references.pmid: 19028840
references.citation: Am J Physiol Heart Circ Physiol. 2006 Aug;291(2):H591-9
references.pmid: 16517944
references.citation: Am J Physiol. 1994 Jan;266(1 Pt 1):L61-83
references.pmid: 7508201
references.citation: Biol Res Nurs. 2005 Apr;6(4):281-8
references.pmid: 15788737
references.citation: Am J Physiol Heart Circ Physiol. 2005 Jun;288(6):H2869-77
references.pmid: 15665052
references.citation: Chest. 1993 Feb;103(2):565-75
references.pmid: 8432155
references.citation: Blood. 1999 Mar 1;93(5):1464-76
references.pmid: 10029572
references.citation: J Cereb Blood Flow Metab. 2004 Aug;24(8):907-15
references.pmid: 15362721
references.citation: Am J Physiol Heart Circ Physiol. 2002 Dec;283(6):H2420-30
references.pmid: 12388263
references.citation: Am J Physiol. 1993 Nov;265(5 Pt 2):H1623-8
references.pmid: 7902014
references.citation: Inflammation. 1992 Aug;16(4):307-14
references.pmid: 1326481
references.citation: Magn Reson Med. 1987 Nov;5(5):466-70
references.pmid: 3431408
references.citation: Arterioscler Thromb Vasc Biol. 2003 Apr 1;23(4):675-80
references.pmid: 12615684
references.citation: Clin Sci (Lond). 1998 May;94(5):461-71
references.pmid: 9682667
references.citation: Physiol Rev. 1999 Jul;79(3):703-61
references.pmid: 10390517
references.citation: Am J Physiol Heart Circ Physiol. 2000 Feb;278(2):H435-43
references.pmid: 10666073
references.citation: Am J Physiol. 1998 Oct;275(4):H1138-47
references.pmid: 9746460
references.citation: Inflammation. 1991 Oct;15(5):331-46
references.pmid: 1684573
references.citation: Blood. 1998 Jan 15;91(2):484-90
references.pmid: 9427701
references.citation: Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1331-8
references.pmid: 15498822
references.citation: Exp Mol Med. 2009 Apr 30;41(4):217-25
references.pmid: 19372727
references.citation: Nat Med. 2003 Jan;9(1):61-7
references.pmid: 12483207
references.citation: Am J Pathol. 1998 Jun;152(6):1463-76
references.pmid: 9626051
references.citation: J Exp Med. 2006 Jun 12;203(6):1519-32
references.pmid: 16754715
references.citation: Am J Physiol. 1990 Jan;258(1 Pt 1):G158-63
references.pmid: 2301577
references.citation: Circ Res. 2004 Feb 6;94(2):239-44
references.pmid: 14670846
references.citation: Biosci Rep. 1992 Apr;12(2):123-33
references.pmid: 1421055
references.citation: Am J Physiol. 1999 Aug;277(2):H569-75
references.pmid: 10444481
references.citation: Am J Physiol Heart Circ Physiol. 2009 Apr;296(4):H1096-107
references.pmid: 19201997
references.citation: Microcirculation. 1999 Mar;6(1):3-5
references.pmid: 10100185
references.citation: Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H365-72
references.pmid: 16155097
references.citation: Curr Med Res Opin. 2002;18 Suppl 2:s18-22
references.pmid: 12365824
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Nov;293(5):G1054-60
references.pmid: 17884975
references.citation: J Cell Biol. 1996 Oct;135(2):497-510
references.pmid: 8896605
references.citation: Microcirculation. 2000 Dec;7(6 Pt 1):367-84
references.pmid: 11142334
references.citation: Br J Exp Pathol. 1964 Dec;45:627-33
references.pmid: 14245163
references.citation: Am J Physiol Gastrointest Liver Physiol. 2003 Jan;284(1):G123-9
references.pmid: 12388188
references.citation: Circ Res. 2000 Dec 8;87(12):1141-8
references.pmid: 11110771
references.citation: West J Med. 1991 Oct;155(4):365-9
references.pmid: 1685284
references.citation: Tissue Cell. 1986;18(1):1-12
references.pmid: 2421456
references.citation: Microvasc Res. 1988 Jan;35(1):27-47
references.pmid: 2830471
references.citation: Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1895-900
references.pmid: 14715510
references.citation: Am J Physiol. 1999 Jan;276(1):H333-9
references.pmid: 9887048
references.citation: Am J Physiol. 1991 Dec;261(6 Pt 2):H1872-9
references.pmid: 1684268
references.citation: FEBS Lett. 1998 Nov 13;439(1-2):147-51
references.pmid: 9849896
references.citation: Blood. 1996 Dec 1;88(11):4330-7
references.pmid: 8943870
references.citation: Am J Physiol Heart Circ Physiol. 2003 Jul;285(1):H406-17
references.pmid: 12649070
references.citation: J Immunol. 2007 May 1;178(9):5940-8
references.pmid: 17442978
references.citation: Circ Res. 2007 Jun 22;100(12):1673-85
references.pmid: 17585075
references.citation: Am J Physiol Cell Physiol. 2002 Dec;283(6):C1745-51
references.pmid: 12388068
references.citation: Circ Res. 1990 May;66(5):1436-44
references.pmid: 2159391
references.citation: Am J Physiol Cell Physiol. 2009 Apr;296(4):C848-56
references.pmid: 19176758
references.citation: J Cell Biol. 1998 Jan 26;140(2):403-7
references.pmid: 9442115
references.citation: Semin Thromb Hemost. 2007 Mar;33(2):123-7
references.pmid: 17340459
references.citation: Am J Physiol. 1990 Nov;259(5 Pt 1):G859-64
references.pmid: 2240225
references.citation: Am J Physiol Heart Circ Physiol. 2000 Mar;278(3):H755-61
references.pmid: 10710343
references.citation: Microcirculation. 1999 Mar;6(1):7-22
references.pmid: 10100186
references.citation: Microcirculation. 2005 Apr-May;12(3):275-85
references.pmid: 15814436
references.citation: Am J Physiol Gastrointest Liver Physiol. 2003 Jun;284(6):G1027-33
references.pmid: 12736150
references.citation: Am J Physiol. 1995 Feb;268(2 Pt 1):L263-9
references.pmid: 7864147
references.citation: Microvasc Res. 1989 Jan;37(1):53-69
references.pmid: 2537922
references.citation: J Immunol. 2001 Aug 15;167(4):2323-30
references.pmid: 11490021
references.citation: Blood. 1988 Apr;71(4):1100-7
references.pmid: 2451547
references.citation: Lab Invest. 1994 May;70(5):684-95
references.pmid: 7910874
references.citation: J Exp Med. 2003 Jan 6;197(1):41-9
references.pmid: 12515812
references.citation: Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H969-H977
references.pmid: 18641276
references.citation: Circ Res. 1988 Apr;62(4):732-40
references.pmid: 2450695
references.citation: Am J Physiol. 1987 Sep;253(3 Pt 2):H699-703
references.pmid: 3631303
references.citation: Eur J Pharmacol. 1984 Oct 15;105(3-4):309-15
references.pmid: 6510472
references.citation: Microcirculation. 2009 Jan;16(1):84-96
references.pmid: 19115139
references.citation: Blood. 1996 Jul 1;88(1):146-57
references.pmid: 8704169
references.citation: Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H898-906
references.pmid: 18515648
references.citation: J Cell Biol. 1992 Feb;116(4):1007-17
references.pmid: 1346398
references.citation: Cardiovasc Res. 2010 May 1;86(2):174-82
references.pmid: 20053659
references.citation: Am J Physiol. 1988 May;254(5 Pt 2):H823-7
references.pmid: 3364586
references.citation: J Immunol. 2004 Aug 1;173(3):2068-77
references.pmid: 15265942
references.citation: Am J Physiol. 1998 Mar;274(3):H1009-15
references.pmid: 9530215
references.citation: Cardiovasc Res. 2010 May 1;86(2):202-10
references.pmid: 20068003
references.citation: Trends Biochem Sci. 1995 Sep;20(9):362-7
references.pmid: 7482704
references.citation: PLoS One. 2008 Feb 20;3(2):e1649
references.pmid: 18297135
references.citation: Clin Exp Immunol. 2005 Apr;140(1):65-72
references.pmid: 15762876
references.citation: J Cell Biol. 2004 Oct 25;167(2):377-88
references.pmid: 15504916
references.citation: Am Rev Respir Dis. 1989 Aug;140(2):294-301
references.pmid: 2764364