title: Neutrophil dependence of vascular remodeling after Mycoplasma infection of mouse airways.
abstract: Vascular remodeling is a feature of sustained inflammation in which capillaries enlarge and acquire the phenotype of venules specialized for plasma leakage and leukocyte recruitment. We sought to determine whether neutrophils are required for vascular remodeling in the respiratory tract by using Mycoplasma pulmonis infection as a model of sustained inflammation in mice. The time course of vascular remodeling coincided with the influx of neutrophils during the first few days after infection and peaked at day 5. Depletion of neutrophils with antibody RB6-8C5 or 1A8 reduced neutrophil influx and vascular remodeling after infection by about 90%. Similarly, vascular remodeling after infection was suppressed in Cxcr2(-/-) mice, in which neutrophils adhered to the endothelium of venules but did not extravasate into the tissue. Expression of the venular adhesion molecule P-selectin increased in endothelial cells from day 1 to day 3 after infection, as did expression of the Cxcr2-receptor ligands Cxcl1 and Cxcl2. Tumor necrosis factor α (TNFα) expression increased more than sixfold in the trachea of wild-type and Cxcr2(-/-) mice, but intratracheal administration of TNFα did not induce vascular remodeling similar to that seen in infection. We conclude that neutrophil influx is required for remodeling of capillaries into venules in the airways of mice with Mycoplasma infection and that TNFα signaling is necessary but not sufficient for vascular remodeling.
authors.affiliation: Cardiovascular Research Institute, Department of Anatomy, and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Electronic address: peter.baluk@ucsf.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Baluk
authors.affiliation: Cardiovascular Research Institute, Department of Anatomy, and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
authors.forename: Keeley
authors.initials: K
authors.lastname: Phillips
authors.affiliation: Cardiovascular Research Institute, Department of Anatomy, and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
authors.forename: Li-Chin
authors.initials: LC
authors.lastname: Yao
authors.affiliation: Cardiovascular Research Institute, Department of Anatomy, and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
authors.forename: Alicia
authors.initials: A
authors.lastname: Adams
authors.affiliation: Cardiovascular Research Institute, Department of Anatomy, and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Nitschké
authors.affiliation: Cardiovascular Research Institute, Department of Anatomy, and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
authors.forename: Donald M
authors.initials: DM
authors.lastname: McDonald
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D009175:Mycoplasma Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045803:Mycoplasma pulmonis; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism* / Q000473:pathology; D066253:Vascular Remodeling
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D023063:Receptors, Interleukin-8B
references.citation: J Immunol. 2012 Apr 1;188(7):3371-81
references.pmid: 22371396
references.citation: Am J Pathol. 2001 Jun;158(6):2043-55
references.pmid: 11395382
references.citation: Am J Pathol. 2010 Mar;176(3):1525-41
references.pmid: 20093490
references.citation: J Biol Chem. 1995 Aug 18;270(33):19402-7
references.pmid: 7642621
references.citation: J Allergy Clin Immunol. 2005 Dec;116(6):1256-63
references.pmid: 16337454
references.citation: J Clin Invest. 2009 Oct;119(10):2954-64
references.pmid: 19759514
references.citation: Immunol Rev. 2011 Nov;244(1):5-8
references.pmid: 22017427
references.citation: Blood. 2004 Jun 1;103(11):4150-6
references.pmid: 14976056
references.citation: Am J Pathol. 2010 Apr;176(4):2009-18
references.pmid: 20133818
references.citation: Exp Lung Res. 2004 Sep;30(6):479-93
references.pmid: 15524406
references.citation: Am J Physiol Lung Cell Mol Physiol. 2006 Dec;291(6):L1232-45
references.pmid: 16891393
references.citation: Nat Rev Immunol. 2010 Jun;10(6):427-39
references.pmid: 20498669
references.citation: Cytokine Growth Factor Rev. 2005 Dec;16(6):593-609
references.pmid: 16046180
references.citation: Microcirculation. 2003 Jan;10(1):99-111
references.pmid: 12610666
references.citation: Am J Pathol. 1998 Oct;153(4):1099-112
references.pmid: 9777941
references.citation: J Clin Invest. 2006 Mar;116(3):695-702
references.pmid: 16485040
references.citation: J Clin Invest. 2005 Feb;115(2):247-57
references.pmid: 15668734
references.citation: Blood. 2011 Nov 3;118(18):4767-8
references.pmid: 22053174
references.citation: Microsc Res Tech. 2002 Jan 1;56(1):15-31
references.pmid: 11810703
references.citation: Chest. 2002 Jun;121(6):1782-8
references.pmid: 12065339
references.citation: Mol Med. 2011 Mar-Apr;17(3-4):293-307
references.pmid: 21046059
references.citation: Proc Am Thorac Soc. 2011 Nov;8(6):504-7
references.pmid: 22052927
references.citation: Proc Natl Acad Sci U S A. 1987 Aug;84(15):5277-81
references.pmid: 2440047
references.citation: J Immunol. 2005 Nov 15;175(10):6319-26
references.pmid: 16272283
references.citation: Nat Rev Immunol. 2013 Mar;13(3):159-75
references.pmid: 23435331
references.citation: Nat Rev Mol Cell Biol. 2010 May;11(5):366-78
references.pmid: 20414258
references.citation: Infect Immun. 2002 Feb;70(2):649-54
references.pmid: 11796594
references.citation: J Leukoc Biol. 2008 Jan;83(1):64-70
references.pmid: 17884993
references.citation: Br J Dermatol. 2007 Jun;156(6):1224-9
references.pmid: 17459047
references.citation: Microcirculation. 2005 Jan-Feb;12(1):47-58
references.pmid: 15804973
references.citation: J Exp Med. 2010 Dec 20;207(13):2975-87
references.pmid: 21149548
references.citation: Nat Med. 2006 Feb;12(2):235-9
references.pmid: 16462802
references.citation: Biochem Biophys Res Commun. 2000 Mar 16;269(2):361-5
references.pmid: 10708557
references.citation: Trends Immunol. 2011 Oct;32(10):461-9
references.pmid: 21839681
references.citation: J Appl Physiol (1985). 2004 Nov;97(5):1999-2004
references.pmid: 15475558
references.citation: Infect Dis Clin North Am. 2010 Mar;24(1):57-60
references.pmid: 20171545
references.citation: Nature. 2013 Jun 20;498(7454):371-5
references.pmid: 23708969
references.citation: Nature. 2011 May 19;473(7347):298-307
references.pmid: 21593862
references.citation: Am J Pathol. 1976 Jan;82(1):157-70
references.pmid: 1247083
references.citation: Pediatr Infect Dis J. 2014 Jan;33(1):92-4
references.pmid: 24346598
references.citation: J Immunol. 2012 Jun 15;188(12):6287-99
references.pmid: 22566565
references.citation: Am J Pathol. 1973 Jul;72(1):63-90
references.pmid: 4719529
references.citation: Trends Immunol. 2011 Oct;32(10):452-60
references.pmid: 21839682
references.citation: J Innate Immun. 2013;5(4):348-57
references.pmid: 23257511
references.citation: Am J Pathol. 1993 Oct;143(4):1009-15
references.pmid: 8213996
references.citation: Nat Rev Immunol. 2011 Jul 25;11(8):519-31
references.pmid: 21785456
references.citation: Am J Pathol. 1977 Nov;89(2):277-96
references.pmid: 920776
references.citation: J Clin Invest. 1989 Jul;84(1):92-9
references.pmid: 2472431
references.citation: J Invest Dermatol. 2000 Aug;115(2):234-44
references.pmid: 10951241
references.citation: J Exp Med. 2013 Jul 1;210(7):1283-99
references.pmid: 23825232
references.citation: Cardiovasc Res. 2010 Jul 15;87(2):281-90
references.pmid: 20472564
references.citation: Am Rev Respir Dis. 1992 Nov;146(5 Pt 2):S40-4
references.pmid: 1443906
references.citation: Am J Pathol. 1990 Dec;137(6):1353-63
references.pmid: 2260625
references.citation: Nat Rev Immunol. 2007 Sep;7(9):678-89
references.pmid: 17717539
references.citation: Science. 1994 Jul 29;265(5172):682-4
references.pmid: 8036519
references.citation: Nat Rev Mol Cell Biol. 2009 Mar;10(3):165-77
references.pmid: 19234476
references.citation: Clin Exp Pharmacol Physiol. 2000 Oct;27(10):836-41
references.pmid: 11022979
references.citation: J Exp Med. 2006 Dec 25;203(13):2907-17
references.pmid: 17158962
references.citation: Am J Pathol. 1978 May;91(2):229-42
references.pmid: 645826
references.citation: Am J Pathol. 2010 Dec;177(6):3233-43
references.pmid: 20952594
references.citation: Nat Rev Cancer. 2003 Jun;3(6):401-10
references.pmid: 12778130
references.citation: Am J Physiol. 1994 Jan;266(1 Pt 1):L61-83
references.pmid: 7508201
references.citation: Am J Pathol. 1998 Oct;153(4):1035-9
references.pmid: 9777935
references.citation: Ann N Y Acad Sci. 1997 Dec 15;832:233-42
references.pmid: 9704051
references.citation: Am J Physiol Heart Circ Physiol. 2004 Jul;287(1):H187-95
references.pmid: 15210451
references.citation: Am J Respir Crit Care Med. 1997 Jul;156(1):229-33
references.pmid: 9230753
references.citation: Open Biol. 2012 Nov;2(11):120134
references.pmid: 23226600