title: Norepinephrine enhances adhesion of HIV-1-infected leukocytes to cardiac microvascular endothelial cells.
abstract: Recent reports have indicated that norepinephrine (NE) enhances HIV replication in infected monocytes and promotes increased expression of select matrix metalloproteinases associated with dilated cardiomyopathy (DCM) in vitro in co-cultures of HIV-infected leukocytes and human cardiac microvascular endothelial cells (HMVEC-C). The influence of NE on HIV infection and leukocyte-endothelial interactions suggests a pathogenic role in AIDS-related cardiovascular disease. This study examined the effects of norepinephrine (NE) and HIV-1 infection on leukocyte adhesion to HMVEC-C. Both flow and static conditions were examined and the expression of selected adhesion molecules and cytokines were monitored in parallel. NE pretreatment resulted in a detectable, dose-dependent increase of leukocyte-endothelial adhesion (LEA) with both HIV-1-infected and -uninfected peripheral blood mononuclear cells (PBMCs) relative to media controls after 48 hr in co-culture with HMVEC-C in vitro. However, the combination of NE plus HIV infection resulted in a significant (P < 0.0001) 18-fold increase in LEA over uninfected media controls. Increased levels in both cell-associated and -soluble ICAM-1 and E-Selectin but not VCAM-1 correlated with increased LEA and with HIV-1 infection or NE pretreatment. Blocking antibodies specific for ICAM-1 or E-Selectin inhibited HIV-NE-induced LEA. These data suggest a model in which NE primes HIV-1-infected leukocytes for enhanced adhesion and localization in HMVEC-C where they can initiate and participate in vascular injury associated with AIDS-related cardiomyopathy.
authors.affiliation: Department of Pathology, Emory University, Atlanta, Georgia 30322, USA. jsundst@emory.edu
authors.forename: J B
authors.initials: JB
authors.lastname: Sundstrom
authors.forename: D E
authors.initials: DE
authors.lastname: Martinson
authors.forename: M
authors.initials: M
authors.lastname: Mosunjac
authors.forename: P
authors.initials: P
authors.lastname: Bostik
authors.forename: L K
authors.initials: LK
authors.lastname: McMullan
authors.forename: R M
authors.initials: RM
authors.lastname: Donahoe
authors.forename: M B
authors.initials: MB
authors.lastname: Gravanis
authors.forename: A A
authors.initials: AA
authors.lastname: Ansari
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology*; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008833:Microcirculation; D009638:Norepinephrine / Q000494:pharmacology*; D010641:Phenotype
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D009638:Norepinephrine