title: HIV-1 infection alters monocyte interactions with human microvascular endothelial cells.
abstract: HIV infection of monocytes resulted in twofold elevation of adhesion molecule LFA-1 (both alpha L/CD11a and beta 2/CD18 subunits) and LFA-3 (CD58), with no apparent increase in LFA-2 (CD2) or various beta 1-integrins. Homotypic aggregation of monocytes was evident 2 h after exposure to virus and was inhibited by mAbs to both the alpha L- and beta 2-subunits of LFA-1. HIV-infected monocytes also showed a marked increase in adherence to human capillary endothelial cell monolayers derived from brain, lung, and skin. This adherence was inhibited by mAb to either LFA-1 subunit and by mAb to the counter-receptor intercellular adhesion molecule-1. Cocultivation of HIV-infected monocytes with endothelial cells increased permeability of endothelial cell monolayers to 125I albumin in transwell assay systems. The increased endothelial permeability induced by HIV-infected monocytes was associated with a substantial disruption of the endothelial cell monolayer. Morphologic disruption was not a direct toxic effect on endothelial cells, but appeared to be secondary to changes in endothelial cell-cell or cell-matrix interactions. Northern blot analysis showed increased expression of gelatinase B (92-kDa gelatinase), tissue inhibitor of metalloproteinase TIMP-1, and TIMP-2 in the HIV-infected monocytes. Consistent with these Northern analyses, secretion of gelatinase activity in culture fluids of HIV-infected monocytes was also increased and was dependent on the stage of virus replication. Incubation of HIV-infected monocytes with the proteinase inhibitors TIMP-1 and TIMP-2 inhibited the increased permeability of endothelial cell monolayers to 125I albumin. These results suggest possible mechanisms for extravasation of HIV-infected monocytes through vascular endothelium into tissue in early stages of HIV disease.
authors.affiliation: Division of Transfusion Transmitted Diseases, Food and Drug Administration, Rockville, MD 20852.
authors.forename: S
authors.initials: S
authors.lastname: Dhawan
authors.forename: B S
authors.initials: BS
authors.lastname: Weeks
authors.forename: C
authors.initials: C
authors.lastname: Soderland
authors.forename: H W
authors.initials: HW
authors.lastname: Schnaper
authors.forename: L A
authors.initials: LA
authors.lastname: Toro
authors.forename: S P
authors.initials: SP
authors.lastname: Asthana
authors.forename: I K
authors.initials: IK
authors.lastname: Hewlett
authors.forename: W G
authors.initials: WG
authors.lastname: Stetler-Stevenson
authors.forename: S S
authors.initials: SS
authors.lastname: Yamada
authors.forename: K M
authors.initials: KM
authors.lastname: Yamada
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D018821:CD18 Antigens / Q000096:biosynthesis / Q000235:genetics; D018968:CD58 Antigens; D002196:Capillaries; D002199:Capillary Permeability; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D018093:Gelatinases / Q000096:biosynthesis / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000473:pathology / Q000821:virology*; D009928:Organ Specificity; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases
chemical_list: D015703:Antigens, CD; D018821:CD18 Antigens; D018968:CD58 Antigens; D006023:Glycoproteins; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D011506:Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases