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Autophagy as a hallmark of hemophagocytic diseases (pp.45-60) $100.00
Authors:  (E. Marion Schneider, Myriam Lorenz, Paul Walther)
Abstract:
Background: Hemophagocytosis occurs in states of genetic and transient immune deficiencies including virus infections, toxicities, malignancies, autoimmune diseases and severe bacterial infections such as sepsis. The documentation of hemophagocytosis in blood and bone marrow smears or organ biopsies is often difficult.
Procedure: It is demonstrated that hemophagocytes can be successfully enriched from Ficoll-separated blood cells by cell culture methods. Isolates from classical hemophagocytic lymphohistiocytosis (HLH patients) and patients with sepsis were compared. High-pressure freezing techniques were applied to study morphological characteristics on the ultrastructural level, and surface markers were studied by flow cytometry.
Results: Hemophagocytosis of autologous blood cells, long-term survival, and the apparently retarded degradation of phagocytosed cells were found in both HLH and sepsis derived cultures. Macroautophagy of cytoplasm and mitochondria was prominent in early cultures and progressed during prolonged cell culture. The structure of the nuclei in both diseases was different, however, HLH hemophagocyte nuclei were polymorph in shape and highly flexible, sepsis-associated hemophagocyte nuclei were round and rigid. Phenotypically, both types of hemophagocytes expressed a similar pattern of largely immature dendritic cell markers. However, the HLH hemophagocytes more often lacked TLR3, whereas the sepsis-derived hemophagocytes were TLR3 positive.
Conclusion: Ultrastructural studies substantiate phagocytosis of autologous erythrocytes and morphologically intact leukocytes in enriched hemophagocyte cultures from patients with HLH and defined cases of sepsis-associated hemophagocytosis. Autophagy is a characteristic feature of these hemophagocytes, which may explain apoptosis resistance in vitro and in vivo. 


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Autophagy as a hallmark of hemophagocytic diseases (pp.45-60)