Impaired macrophage phagocytosis of apoptotic neutrophils in patients with human immunodeficiency virus type 1 infection.
Dysfunction of neutrophils (polymorphonuclear leukocytes [PMNL]) and macrophagic cells occurs as a consequence of human immunodeficiency virus type 1 (HIV-1) infection. Macrophages contribute to the resolution of early inflammation ingesting PMNL apoptotic bodies. This study investigated macrophage ability to phagocytose PMNL apoptotic bodies in patients with HIV-1 infection in comparison with uninfected individuals and the effect of HIV Nef protein on apoptotic body phagocytosis to determine if phagocytic activity is impaired by HIV infection. Monocytes/macrophages were isolated from 10 HIV-1-infected patients and from five healthy volunteers, whereas PMNL were isolated from healthy volunteers. Macrophage phagocytosis of apoptotic PMNL was determined by staining of apoptotic bodies with fluorescein-conjugated concanavalin A or with fluorescein-labeled phalloidin. Our data show significant impairment of PMNL apoptotic body macrophage phagocytosis in subjects with HIV-1 infection presenting a concentration of CD4(+) T lymphocytes of >200/mm(3) and in particular in those with <200 CD4(+) T lymphocyte cells/mm(3). In addition, HIV-1 recombinant Nef protein is able to decrease phagocytosis of apoptotic PMNL from normal human macrophages in a dose-dependent manner. The results of our study suggest that impaired macrophage phagocytosis of PMNL apoptotic bodies may contribute to the persistence of the inflammatory state in HIV-infected subjects, especially during opportunistic infections that are often favored by defective phagocytic activity.
Section of Pediatric Infectious Diseases, Regional Hospital, Varese, Italy. eiwlw@tin.it
Donato
D
Torre
Luisa
L
Gennero
F M
FM
Baccino
Filippo
F
Speranza
Gilberto
G
Biondi
Agostino
A
Pugliese
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D015693:Gene Products, nef / Q000276:immunology / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D009504:Neutrophils / Q000276:immunology* / Q000821:virology; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus