TY - JOUR
T1 - Accelerated neutrophil apoptosis in the acquired immunodeficiency syndrome
AU - Pitrak, David L.
AU - Tsai, Ho Chie
AU - Mullane, Kathleen M.
AU - Sutton, Sarah H.
AU - Stevens, Paul
PY - 1996/12/15
Y1 - 1996/12/15
N2 - Neutrophil (PMNL) function defects occur as a consequence of HIV infection. This study examined PMNL apoptosis in patients with the acquired immunodeficiency syndrome (AIDS) to determine if accelerated apoptosis contributes to impaired function. PMNL were isolated from 10 HIV-infected patients with CD4+ lymphocyte counts < 200/mm3 without signs of active infection and 7 healthy volunteers. PMNL were stained with acridine orange and ethidium bromide after 0, 3, 6, and 18 h in culture, and examined for the morphologic changes of apoptosis and viability by fluorescent microscopy. Apoptosis was also demonstrated by electron microscopy, flow cytometry, and DNA gel electrophoresis. Apoptosis was minimal at 0 h, but PMNL from AIDS patients exhibited significantly greater apoptosis than controls at 3h (22.5±11.5 vs. 8.9±6.9%, P = 0.015), 6 h (38.1±14.2 vs. 18.1±4.5%, P = 0.003), and 18 h (71.3±19.0 vs. 38.8± 16.7%, P = 0.002). Viabilities were ≤ 88.0% for both groups from 0-6 h, but by 18 h viability was significantly decreased for the HIV group (58.8±12.4 vs. 83.5±10.4%, P = 0.001) due to an increase in non-viable apoptotic cells. Incubation with serum from AIDS patients had no effect on control PMNL, and incubation with control serum did not reduce the rate of apoptosis of PMNL from AIDS patients. Incubation with granulocyte colony-stimulating factor (G-CSF) in vitro significantly decreased apoptosis for PMNL from AIDS patients. PMNL from patients with AIDS exhibit markedly accelerated apoptosis ex vivo. In vivo, apoptosis and functional impairment of PMNL may contribute to the risk of secondary infections, and cytokine therapy may be of potential clinical benefit in this circumstance.
AB - Neutrophil (PMNL) function defects occur as a consequence of HIV infection. This study examined PMNL apoptosis in patients with the acquired immunodeficiency syndrome (AIDS) to determine if accelerated apoptosis contributes to impaired function. PMNL were isolated from 10 HIV-infected patients with CD4+ lymphocyte counts < 200/mm3 without signs of active infection and 7 healthy volunteers. PMNL were stained with acridine orange and ethidium bromide after 0, 3, 6, and 18 h in culture, and examined for the morphologic changes of apoptosis and viability by fluorescent microscopy. Apoptosis was also demonstrated by electron microscopy, flow cytometry, and DNA gel electrophoresis. Apoptosis was minimal at 0 h, but PMNL from AIDS patients exhibited significantly greater apoptosis than controls at 3h (22.5±11.5 vs. 8.9±6.9%, P = 0.015), 6 h (38.1±14.2 vs. 18.1±4.5%, P = 0.003), and 18 h (71.3±19.0 vs. 38.8± 16.7%, P = 0.002). Viabilities were ≤ 88.0% for both groups from 0-6 h, but by 18 h viability was significantly decreased for the HIV group (58.8±12.4 vs. 83.5±10.4%, P = 0.001) due to an increase in non-viable apoptotic cells. Incubation with serum from AIDS patients had no effect on control PMNL, and incubation with control serum did not reduce the rate of apoptosis of PMNL from AIDS patients. Incubation with granulocyte colony-stimulating factor (G-CSF) in vitro significantly decreased apoptosis for PMNL from AIDS patients. PMNL from patients with AIDS exhibit markedly accelerated apoptosis ex vivo. In vivo, apoptosis and functional impairment of PMNL may contribute to the risk of secondary infections, and cytokine therapy may be of potential clinical benefit in this circumstance.
KW - DNA
KW - HIV
KW - cell death
KW - cytokines
KW - granulocyte colony-stimulating factor
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U2 - 10.1172/JCI119096
DO - 10.1172/JCI119096
M3 - Article
C2 - 8981916
AN - SCOPUS:12644272783
VL - 98
SP - 2714
EP - 2719
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 12
ER -