title: Macrophage inflammatory protein-1alpha is induced by human immunodeficiency virus infection of monocyte-derived macrophages.
abstract: Disparate findings have been reported as to whether human immunodeficiency virus (HIV) affects cytokine production by macrophages (MA). We investigated production of different cytokines and of macrophage inflammatory protein (MIP)-1alpha by HIV-1Ba-L- or HIV-1Ada-infected blood-derived MA. Relative to controls, only MIP-1alpha levels increased twofold to > 10-fold in supernatants 2 to 3 weeks postinfection (PI), at the time of maximum virus production; levels of the other chemokines (RANTES, interleukin (IL)-8) and cytokines (IL-1alpha, IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1) investigated were not affected. MIP-1alpha mRNA signal assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) was, however, only occasionally greater in cells from infected cultures relative to controls. MIP-1alpha levels in supernatants remained in the same range as in control cultures when more than 10 mmol/L Zidovudine was added 24 hours PI, which indicates involvement of virus replication in the effect. Anti-MIP-1alpha antibody labeling identified a 10% to 25% subset of MA, strongly expressing HLA-DR and CD4, and also stained by anti-IL-6 and anti-TNF-alpha antibodies. Two weeks PI, dual staining showed that the majority of the 5% to 20% cells that were p24+ belonged to the MIP-1alpha+ population, which may define a MA subset capable to better sustain HIV replication. MIP-1alpha induced by HIV replication in MA might play a role in the pathophysiology of HIV infection; in impaired hematopoiesis; or as a CD4+ and CD8+ lymphocyte chemoattractant, by recruiting either or both HIV-susceptible and cytotoxic T lymphocytes to virus replication sites.
authors.affiliation: Laboratoire de Biologie et Génétique des Déficits Immunitaires, faculté de Médecine and hôpital de la Pitié-Salpétrière, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Canque
authors.forename: M
authors.initials: M
authors.lastname: Rosenzwajg
authors.forename: A
authors.initials: A
authors.lastname: Gey
authors.forename: E
authors.initials: E
authors.lastname: Tartour
authors.forename: W H
authors.initials: WH
authors.lastname: Fridman
authors.forename: J C
authors.initials: JC
authors.lastname: Gluckman
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019402:Macrophage Inflammatory Proteins; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D008969:Molecular Sequence Data; D009000:Monocytes; D015846:Monokines / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D012333:RNA, Messenger; D015215:Zidovudine