Human neutrophils lose their surface Fc gamma RIII and acquire Annexin V binding sites during apoptosis in vitro

Homburg, Christa; Haas, Masja de; Borne, A. E. G. K. Von Dem; Verhoeven, A. J.; Reutelingsperger, Chris; Roos, Dirk

doi:10.1182/blood.v85.2.532.532

Cited by 390 publications

(121 citation statements)

References 30 publications

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“…2 and 3). A time overlap between nuclear changes (DNA fragmentation, chromatin condensation) and PS exposure has been observed by others (37)(38)(39). The simultaneous appearance of AV( +)/PI( +) and AV( +)/PI( -) cell subpopulations in U937 cells has been shown by Fabisiak et al (40) in murine cell lines, suggesting that cells are undergoing apoptosis, as well as necrosis.…”

Section: Discussionmentioning

confidence: 71%

Association of Ceramide Accumulation with Photodynamic Treatment-Induced Cell Death

Šeparović¹,

Mann²,

Oleinick³

1998

Photchem. Photbio.

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Ceramide, a stress-induced second messenger, has been associated with apoptosis in several malignant and non-malignant cell lines. We have shown that photodynamic treatment (PDT), using the phthalocyanine photosensitizer Pc 4 (HOSiPcOSi[CH3]2[CH2]3N[CH3]2), causes increased ceramide generation and subsequent induction of apoptosis in L5178Y-R (LY-R) mouse lymphoma cells. To test further if ceramide generation accompanies photocytotoxicity, we treated various cell lines with a PDT dose producing a 99-99.9% loss of clonogenicity. Like LY-R cells, human leukemia (U937) cells underwent rapid DNA fragmentation initiating within 1 h after PDT. Similarly, Chinese hamster ovary (CHO) cells showed rapid DNA laddering, beginning 1 h following the treatment. In contrast, mouse radiation-induced fibrosarcoma (RIF-1) cells showed no apoptosis within 24 h post-PDT, as judged by the absence of 50 kbp and oligonucleosome size DNA fragments, as well as no annexin V binding to cells with preserved membrane integrity. Using the same doses of PDT, we observed a time-dependent ceramide accumulation in all three cell lines. While a significant increase in ceramide levels was reached within 1 and 10 min in U937 and CHO cells, respectively, elevated ceramide production was measured only after 30 min in RIF-1 cells. In addition, exogenous N-acetyl-sphingosine was able to mimic PDT-induced apoptosis in U937 and CHO cells. We suggest that ceramide accumulation is associated with PDT-induced apoptosis and photocytotoxicity.

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Section: Discussionmentioning

confidence: 71%

Association of Ceramide Accumulation with Photodynamic Treatment-Induced Cell Death

Šeparović¹,

Mann²,

Oleinick³

1998

Photchem. Photbio.

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“…Neutrophils downregulate a number of membrane proteins as they age, including CD16 (FcγRIII), CD31 (PECAM-1), CD32, CD35 (Complement receptor 1), CD43, CD45, CD44, CD47 (IAP), CD50 (ICAM-3), CD55 (Complement regulatory protein DAF), CD62L (L-selectin), CD63, CD66b, CD87 (uPAR), CD88 (C5a receptor), and CD120a (tumor necrosis factor receptor 1), thus significantly changing the apoptotic neutrophil surface. [35][36][37][38][39][40] Some of these proteins, including CD31 and ICAM-3, are also functionally modified, 41,42 whereas other proteins, including ICAM-1, are upregulated on apoptotic neutrophils. [41][42][43] Finally, new antigens are expressed on the surface of apoptotic neu-…”

Section: Untangling the Phagocytic Synapsementioning

confidence: 99%

Clearance of apoptotic neutrophils and resolution of inflammation

Greenlee‐Wacker

2016

Immunological Reviews

349

299

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Summary The engulfment of apoptotic cells by phagocytes, a process referred to as efferocytosis, is essential for maintenance of normal tissue homeostasis and a prerequisite for the resolution of inflammation. Neutrophils are the predominant circulating white blood cell in humans, and contain an arsenal of toxic substances that kill and degrade microbes. Neutrophils are short lived and spontaneously die by apoptosis. This review will highlight how the engulfment of apoptotic neutrophils by human phagocytes occurs, how heterogeneity of phagocyte populations influences efferocytosis signaling, and downstream consequences of efferocytosis. The efferocytosis of apoptotic neutrophils by macrophages promotes anti-inflammatory signaling, prevents neutrophil lysis, and dampens immune responses. Given the immunomodulatory properties of efferocytosis, understanding pathways that regulate and enhance efferocytosis could be harnessed to combat infection and chronic inflammatory conditions.

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“…As an indicator of neutrophil apoptosis, we analyzed the exposure of phosphatidylserine (PS) on the surface of apoptotic cells by staining with FITC-conjugated annexin V, a calcium-dependent phospholipid-binding protein with high affinity for PS (21). We performed specific binding of annexin V by incubating neutrophils (2 × 10 5 cells) for 30 min at 4 û C in the dark in 60 µl of binding buffer (150 mM NaCl, 2.5 mM CaCl 2 , 10 mM HEPES; pH 7.4) containing a saturating concentration of annexin V. We determined nonspecific binding by using calcium-free binding buffer (150 mM NaCl; 10 mM EDTA; 10 mM HEPES, pH 7.4).…”

Section: Evaluation Of Neutrophil Apoptosis By Flow Cytometrymentioning

confidence: 99%

p38 Mitogen‐activated protein kinase and phosphatidylinositol 3‐kinase activities have opposite effects on human neutrophil apoptosis

Alvarado-Kristensson¹,

Pörn-Ares²,

Grethe³

et al. 2001

FASEB j.

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Neutrophil apoptosis is essential for resolution of inflammatory reactions. Here, we studied the role of two apoptosis/survival-associated protein kinases in this process. We discovered a previously undetected early and transient inhibition of the activity of p38 mitogen-activated protein kinase (p38 MAPK) during both spontaneous and Fas-induced apoptosis. Pharmacological inhibition of this enzyme augmented the activation of caspases and the apoptotic response, which suggests that the p38 MAPK signals survival in neutrophils. Our finding that caspase-3 activity was initiated during the transient inhibition of p38 MAPK suggests that apoptosis is initiated during this inhibition. Furthermore, such transient inhibition was counteracted by granulocyte-macrophage colony-stimulating factor, which elicits survival. We also found that neither this inhibition of p38 MAPK nor the spontaneous apoptotic response depended on Fas. Instead, the early inhibition of p38 MAPK concurred with a Fas-induced activation of phosphatidylinositol 3-kinase, inhibition of which reduced apoptosis. Thus, the Fas-induced augmentation of spontaneous apoptosis can be explained by its activation of phosphatidylinositol 3-kinase. We conclude that p38 MAPK activity represents a survival signal that is inactivated transiently during both spontaneous and Fas-induced apoptosis, whereas Fas-induced phosphatidylinositol 3-kinase activity is a proapoptotic signal in isolated human neutrophils.

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Human neutrophils lose their surface Fc gamma RIII and acquire Annexin V binding sites during apoptosis in vitro

Cited by 390 publications

References 30 publications

Association of Ceramide Accumulation with Photodynamic Treatment-Induced Cell Death

Association of Ceramide Accumulation with Photodynamic Treatment-Induced Cell Death

Clearance of apoptotic neutrophils and resolution of inflammation

p38 Mitogen‐activated protein kinase and phosphatidylinositol 3‐kinase activities have opposite effects on human neutrophil apoptosis

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