title: Rickettsia rickettsii infection of human macrovascular and microvascular endothelial cells reveals activation of both common and cell type-specific host response mechanisms.
abstract: Although inflammation and altered barrier functions of the vasculature, due predominantly to the infection of endothelial cell lining of small and medium-sized blood vessels, represent salient pathological features of human rickettsioses, the interactions between pathogenic rickettsiae and microvascular endothelial cells remain poorly understood. We have investigated the activation of nuclear transcription factor-kappa B (NF-kappaB) and p38 mitogen-activated protein (MAP) kinase, expression of heme oxygenase 1 (HO-1) and cyclooxygenase 2 (COX-2), and secretion of chemokines and prostaglandins after Rickettsia rickettsii infection of human cerebral, dermal, and pulmonary microvascular endothelial cells in comparison with pulmonary artery cells of macrovascular origin. NF-kappaB and p38 kinase activation and increased HO-1 mRNA expression were clearly evident in all cell types, along with relatively similar susceptibility to R. rickettsii infection in vitro but considerable variations in the intensities/kinetics of the aforementioned host responses. As expected, the overall activation profiles of macrovascular endothelial cells derived from human pulmonary artery and umbilical vein were nearly identical. Interestingly, cerebral endothelial cells displayed a marked refractoriness in chemokine production and secretion, while all other cell types secreted various levels of interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) in response to infection. A unique feature of all microvascular endothelial cells was the lack of induced COX-2 expression and resultant inability to secrete prostaglandin E(2) after R. rickettsii infection. Comparative evaluation thus yields the first experimental evidence for the activation of both common and unique cell type-specific host response mechanisms in macrovascular and microvascular endothelial cells infected with R. rickettsii, a prototypical species known to cause Rocky Mountain spotted fever in humans.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Rydkina
authors.forename: Loel C
authors.initials: LC
authors.lastname: Turpin
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Sahni
mesh_terms: D001921:Brain / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000382:microbiology*; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D008168:Lung / Q000276:immunology / Q000382:microbiology; D011453:Prostaglandins / Q000378:metabolism; D012284:Rickettsia rickettsii / Q000276:immunology*; D012867:Skin / Q000276:immunology / Q000382:microbiology
chemical_list: D016207:Cytokines; D011453:Prostaglandins
references.citation: Infect Immun. 2002 Aug;70(8):4045-52
references.pmid: 12117910
references.citation: Infect Immun. 2006 Sep;74(9):5067-74
references.pmid: 16926398
references.citation: Future Microbiol. 2009 Apr;4(3):323-39
references.pmid: 19327117
references.citation: Pharmacol Rev. 2004 Sep;56(3):387-437
references.pmid: 15317910
references.citation: Circulation. 2003 Oct 7;108(14):1676-8
references.pmid: 14504187
references.citation: FASEB J. 1997 Nov;11(13):1187-97
references.pmid: 9367354
references.citation: Arch Neurol. 2002 Mar;59(3):391-7
references.pmid: 11890842
references.citation: Brain Pathol. 2000 Jan;10(1):113-26
references.pmid: 10668901
references.citation: Pharmacol Rep. 2008 Jan-Feb;60(1):139-43
references.pmid: 18276995
references.citation: Cancer Res. 2005 Nov 15;65(22):10347-54
references.pmid: 16288024
references.citation: Infect Immun. 1998 May;66(5):2290-9
references.pmid: 9573120
references.citation: Annu Rev Pathol. 2006;1:171-98
references.pmid: 18039112
references.citation: J Pharmacol Exp Ther. 2001 Jun;297(3):1051-8
references.pmid: 11356928
references.citation: Am J Pathol. 2003 Oct;163(4):1357-69
references.pmid: 14507644
references.citation: PLoS One. 2007 Mar 07;2(3):e266
references.pmid: 17342200
references.citation: J Anat. 2002 Jun;200(6):629-38
references.pmid: 12162730
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4646-51
references.pmid: 9539792
references.citation: Cell Microbiol. 2005 Oct;7(10):1519-30
references.pmid: 16153249
references.citation: Prog Histochem Cytochem. 1988;18(3):1-99
references.pmid: 3055069
references.citation: Infect Immun. 1992 Dec;60(12):5113-8
references.pmid: 1333449
references.citation: Curr Opin Cell Biol. 2009 Apr;21(2):317-24
references.pmid: 19217767
references.citation: Eur Respir J Suppl. 1990 Oct;11:482s-484s
references.pmid: 2278607
references.citation: Clin Vaccine Immunol. 2007 Nov;14(11):1420-4
references.pmid: 17898182
references.citation: Braz J Infect Dis. 2002 Apr;6(2):91-6
references.pmid: 11980610
references.citation: J Med Microbiol. 2007 Jul;56(Pt 7):896-906
references.pmid: 17577053
references.citation: Clin Exp Rheumatol. 2008 May-Jun;26(3 Suppl 49):S135-40
references.pmid: 18799071
references.citation: J Infect Dis. 1984 Feb;149(2):201-6
references.pmid: 6421942
references.citation: Infect Immun. 1998 May;66(5):1827-33
references.pmid: 9573057
references.citation: J Clin Invest. 1995 Dec;96(6):2839-44
references.pmid: 8675654
references.citation: Infect Immun. 1997 Jul;65(7):2786-91
references.pmid: 9199451
references.citation: Int J Med Microbiol. 2005 Aug;295(4):267-78
references.pmid: 16128401
references.citation: Infect Immun. 2003 Jul;71(7):4127-36
references.pmid: 12819104
references.citation: Brain Res. 1982 Jun 3;241(1):49-55
references.pmid: 6980688
references.citation: Am J Trop Med Hyg. 1985 Mar;34(2):361-71
references.pmid: 3885774
references.citation: Infect Immun. 1984 Jun;44(3):545-53
references.pmid: 6724689
references.citation: J Cell Biol. 1967 Jul;34(1):207-17
references.pmid: 6033532
references.citation: Infect Immun. 1998 Mar;66(3):1070-5
references.pmid: 9488397
references.citation: J Clin Immunol. 2008 Mar;28(2):174-85
references.pmid: 17957455
references.citation: J Invest Dermatol. 1992 Dec;99(6):683-90
references.pmid: 1361507