Granulocyte-macrophage colony-stimulating factor augments phagocytosis of Mycobacterium avium complex by human immunodeficiency virus type 1-infected monocytes/macrophages in vitro and in vivo.
The role of human immunodeficiency virus type 1 (HIV-1) infection on the ability of human monocytes/macrophages to phagocytose Mycobacterium avium complex (MAC) in vivo and in vitro and the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on this function were investigated. By use of a flow cytometric assay to quantify phagocytosis, HIV-1 infection was found to impair the ability of monocyte-derived macrophages to phagocytose MAC in vitro, whereas GM-CSF significantly improved this defect. Phagocytosis was not altered by exposure to a mutant form of GM-CSF (E21R) binding only to the alpha chain of the GM-CSF receptor, suggesting that signaling by GM-CSF that leads to augmentation of phagocytosis is via the beta chain of the receptor. In a patient with AIDS and disseminated multidrug-resistant MAC infection, GM-CSF treatment improved phagocytosis of MAC by peripheral blood monocytes and reduced bacteremia. These results imply that GM-CSF therapy may be useful in restoring antimycobacterial function by human monocytes/macrophages.
Kedzierska
K
K
AIDS Pathogenesis Research Unit, Macfarlane Burnet Centre, and National Centre for HIV Virology Research, Fairfield, Australia.
Mak
J
J
Mijch
A
A
Cooke
I
I
Rainbird
M
M
Roberts
S
S
Paukovics
G
G
Jolley
D
D
Lopez
A
A
Crowe
S M
SM
D000328:Adult; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology / Q000821:virology; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000382:microbiology / Q000821:virology; D015269:Mycobacterium avium Complex / Q000276:immunology*; D015270:Mycobacterium avium-intracellulare Infection / Q000150:complications / Q000188:drug therapy; D010587:Phagocytosis / Q000187:drug effects*
D016178:Granulocyte-Macrophage Colony-Stimulating Factor