Human pancreatic islet endothelial cells express coxsackievirus and adenovirus receptor and are activated by coxsackie B virus infection.
Enteroviruses, such as the coxsackievirus (CV) group, have been linked to the induction of inflammatory and autoimmune diseases. Virus tropism and tissue access are modulated by endothelial cells. To examine the susceptibility of microvascular endothelial cells (MECs) derived from pancreatic islets to infection with CV group B (CVB), purified cultured human islet MECs were infected with CVB-4 strain, and the immunological phenotype of the infected cells was analyzed. CVB-4 persistently infected the islet MECs, which expressed the CV receptors human coxsackievirus and adenovirus receptor (HCAR) and decay accelerating factor (DAF) and maintained EC characteristics, without overt cytopathic effects. CVB-4 infection transiently up-regulated expression of the adhesion molecules ICAM-1 and VCAM-1 and increased production of the proinflammatory cytokines IL-1beta and IL-6, and chemokines IL-8 and lymphotactin, as well as IFN-alpha. Mononuclear cell adhesion to CVB infected monolayers was increased, compared to uninfected monolayers. Moreover, infection up-regulated the viral receptors HCAR and DAF and coreceptor alpha(v)beta3 integrin on islet MECs, while down-regulating expression of HCAR on human aortic endothelial cells, indicating potential tissue-specific influence on the pathological outcome of infection. These results provide evidence that islet MECs are natural targets and reservoirs for persistent CVB infection resulting in acute endothelial cell activation by virus, which may contribute to selective recruitment of subsets of leukocytes during inflammatory immune responses, such as insulitis in type 1 diabetes.
Zanone
Maria M
MM
Department of Internal Medicine, University of Torino, Italy. mmz@libero.it
Favaro
Enrica
E
Ferioli
Elena
E
Huang
Guo C
GC
Klein
Nigel J
NJ
Perin
Paolo Cavallo
PC
Peakman
Mark
M
Conaldi
Pier G
PG
Camussi
Giovanni
G
D000818:Animals; D001011:Aorta / Q000166:cytology; D018958:CD55 Antigens / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D003384:Coxsackievirus Infections / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D029822:Enterovirus B, Human / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D007515:Islets of Langerhans / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008833:Microcirculation; D020411:Oligonucleotide Array Sequence Analysis; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*
D018958:CD55 Antigens; C568771:CLMP protein, human; D018925:Chemokines; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D016207:Cytokines; D011991:Receptors, Virus