title: Interleukin 4 and human immunodeficiency virus stimulate LFA-1-ICAM-1-mediated aggregation of monocytes and subsequent giant cell formation.
abstract: The effects of recombinant interleukin 4 (IL-4) on cell cluster and multinucleated giant cell (MGC) formation from human immunodeficiency virus (HIV)-infected and uninfected monocytes were examined. Human blood monocytes were isolated by centrifugal elutriation and monoclonal antibody-complement-dependent lysis of residual T cells, and infected with low passage HIV strains. Monocytes were exposed to recombinant IL-4 (1 to 20 ng/ml), continuously after inoculation with HIV. Monocyte expression of ICAM-1 but not LFA-1 was significantly enhanced by IL-4 although substrate adherence was a more potent stimulus. Monocyte cluster and MGC formation was quantified after fixation and staining with Giemsa. Clusters of HIV-infected and uninfected monocytes were consistently and significantly increased at 4 to 7 days after IL-4 stimulation. The combination of HIV and IL-4 was more stimulatory than either treatment alone. In two out of five uninfected and three out of seven HIV-infected monocyte cultures, MGC formation was also markedly increased at 10 to 14 days after stimulation. Incubation with anti-LFA-1 (anti-CD11a, anti-CD18) and anti-ICAM-1 (anti-CD54) monoclonal antibodies reduced IL-4-stimulated aggregation in HIV-infected and uninfected monocytes and subsequently reduced MGC formation. Anti-ICAM-1 was not as effective as anti-CD11a or anti-CD18 in inhibiting aggregation of HIV-infected monocytes and in these cultures anti-ICAM-2 was also inhibitory. Extracellular HIV antigen concentrations were not consistently reduced by anti-CD11a or anti-ICAM-1. Hence IL-4 markedly enhanced monocyte aggregation in both HIV-infected and uninfected monocytes, probably through enhanced LFA-1-ICAM-1 interactions in all cultures and LFA-1-ICAM-2 interactions in infected monocytes, leading subsequently to MGC formation in some cultures.
authors.affiliation: Department of Virology, ICPMR, Westmead Hospital, Sydney, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Kazazi
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: A
authors.initials: A
authors.lastname: Lopez
authors.forename: M
authors.initials: M
authors.lastname: Vadas
authors.forename: A L
authors.initials: AL
authors.lastname: Cunningham
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D002448:Cell Adhesion; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015726:Giant Cells / Q000187:drug effects / Q000276:immunology; D006678:HIV / Q000276:immunology*; D018023:HIV Seronegativity; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology; D012016:Reference Values; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016169:Lymphocyte Function-Associated Antigen-1; D011991:Receptors, Virus; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4