title: Effects of inflammatory cytokines on the permeability of human lung microvascular endothelial cell monolayers and differential eosinophil transmigration.
abstract: BACKGROUND
  Rhinovirus (RV) infections can result in asthma exacerbations in both adults and children. Respiratory epithelium, the primary site of RV replication, responds to the viral infection by generating a variety of cytokines and chemokines capable of promoting airway inflammation and hence might increase asthma severity. Some of these mediators might also affect the permeability of underlying vascular endothelium.
  
  
  OBJECTIVE
  We hypothesized that RV infections can promote airway inflammation and thus asthma by enhancing local vascular permeability.
  
  
  METHODS
  Confluent human lung microvascular endothelial cell (HMVEC-L) monolayers were used as an in vitro model of vascular endothelium to determine whether cytokines associated with RV-induced infections are capable of modulating endothelial cell permeability as measured by means of transendothelial electrical resistance. Recombinant cytokines and chemokines were added to confluent HMVEC-L monolayers cultured on Transwell filters, and permeability was measured as decreased electrical resistance over time. Eosinophil transendothelial migration was assessed under the same experimental conditions.
  
  
  RESULTS
  TNF- alpha, IL-1 beta, and IFN- gamma significantly increased HMVEC-L permeability. In contrast, GM-CSF, G-CSF, IL-8, IL-6, and RANTES had no effect. Although incubation of HMVEC-L monolayers with either TNF-alpha or IL-1beta promoted eosinophil migration, IFN-gamma had no effect, indicating that enhanced permeability alone was not sufficient for eosinophil infiltration.
  
  
  CONCLUSIONS
  Select cytokines, generated in response to RV infection, can increase vascular permeability and might provide a mechanism by which RV infection can lead to edema, cellular infiltration, and inflammation and thus compromised airflow.
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, University of Wisconsin, Madison, USA.
authors.forename: Julie B
authors.initials: JB
authors.lastname: Sedgwick
authors.forename: Indu
authors.initials: I
authors.lastname: Menon
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
mesh_terms: D001249:Asthma / Q000276:immunology; D002199:Capillary Permeability; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000098:blood supply / Q000166:cytology*; D008833:Microcirculation / Q000166:cytology; D010850:Picornaviridae Infections / Q000276:immunology
chemical_list: D016207:Cytokines