Accelerated neutrophil apoptosis in the acquired immunodeficiency syndrome.

Abstract

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 ϩ lymphocyte counts Ͻ 200/mm 3 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 3 h (22.5 Ϯ 11.5 vs. 8.9 Ϯ 6.9%, P ϭ 0.015), 6 h (38.1 Ϯ 14.2 vs. 18.1 Ϯ 4.5%, P ϭ 0.003), and 18 h (71.3 Ϯ 19.0 vs. 38.8 Ϯ 16.7%, P ϭ 0.002). Viabilities were Ն 88.0% for both groups from 0-6 h, but by 18 h viability was significantly decreased for the HIV group (58.8 Ϯ 12.4 vs. 83.5 Ϯ 10.4%, P ϭ 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. ( J. Clin. Invest. 1996. 98:2714-2719.)

Expression of genes involved in initiation, regulation, and execution of apoptosis in human neutrophils and during neutrophil differentiation of HL-60 cells

“…Neutrophils enter the bloodstream and tissues as terminally differentiated cells, which are unable to self-renew and have the shortest half-life of all circulating leukocytes. After leaving the bone marrow, neutrophils are programmed to die within about 24 h as a result of constitutive and spontaneous apoptosis [3][4][5], a controlled biological process leading to the physiological death of the cell, and characterized by cell shrinkage, chromatin condensation, and internucleosomal DNA degradation, widely considered to be a biochemical hallmark of apoptosis [6].…”

The apoptosis of neutrophils is accelerated in respiratory syncytial virus (RSV)-induced bronchiolitis

“…The modulation of neutrophil apoptosis in RSV infection in vivo may regulate the epithelial damage induced by neutrophils. To date, however, there are no published studies of neutrophil apoptosis in RSV infection, although a recent study shows that HIV infection accelerates neutrophil apoptosis [11].…”

“…On the other hand, because apoptotic neutrophils are functionally impaired [32], accelerated neutrophil apoptosis in vivo may contribute to the risk of secondary infection [11], which has been associated with RSV infection [33,34]. In addition, although in this study neutrophil apoptosis due to RSV infection was investigated, it is likely that other respiratory viral infections could have a similar effect.…”

Exosomes Decrease In Vitro Infectivity of HIV-1 Preparations: Implication for CD4+T Lymphocyte Depletion In Vivo

“…It is well established that dendritic cells (DCs) are involved early in HIV-1 transmission (Granelli-Piperno et al, 1998;Manel et al, 2010;Tsunetsugu-Yokota et al, 1997). It is also known that CD4TL, more particularly the Th17 mucosal subset (Cecchinato and Franchini, 2010;Cecchinato et al, 2008;Elhed and Unutmaz, 2010;Favre et al, 2009;Milush et al, 2011;Paiardini, 2010) are dysregulated (Elbim et al, 2009;Hofman et al, 1999;Okada, Takei, and Tashiro, 1997;Okada, Takei, and Tashiro, 1998;Pitrak et al, 1996;Roilides et al, 1993;Roilides et al, 1990;Szelc et al, 1992;Thorsen, Busch-Sorensen, and Sondergaard, 1989) in pathogenic HIV-1/SIV infection (Brenchley et al, 2008;Elbim et al, 2009;Elbim et al, 2008;Favre et al, 2009). A rapid decrease thus occurs in the numbers of both infected and uninfected CD4TL within the very first weeks of infection.…”