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Nancy Berliner, MD

Professor, Department of Medicine, Harvard Medical School

Senior Attending Physician, Medicine/Hematology, Brigham And Women's Hospital

Contact Info

Nancy Berliner
Brigham and Women's Hospital
75 Francis Street

Boston, MA, 02115
Phone not available.
Email not available

Assistant

Jackie Gifford
Administrative Coordinator
Hematology
Brigham And Women's Hospital
75 Francis Street
Boston, MA, 02115
Phone: 617-732-5840
JGIFFORD3@PARTNERS.ORG

DF/HCC Program Affiliation

Leukemia
Cancer Genetics

Research Abstract

The capacity of neutrophils to eradicate bacterial infections is dependent on normal development and activation of functional responses, which include chemotaxis and generation of oxygen radicals during the respiratory burst. A unique feature of the neutrophil is its highly lobulated nucleus, which is thought to facilitate chemotaxis, but may also play a role in other critical neutrophil functions. Nuclear lobulation is dependent on expression of the inner nuclear envelope protein, the lamin B receptor (LBR), mutations of which cause hypolobulated neutrophil nuclei in human Pelger-Hu√ęt anomaly and the "ichthyosis" (ic) phenotype in mice. In this study, we have investigated roles for LBR in mediating neutrophil development and activation of multiple neutrophil functions, including chemotaxis and the respiratory burst. MATERIALS AND METHODS: A progenitor EML cell line was generated from an ic/ic mouse, and derived cells that lacked LBR expression were induced to mature neutrophils and then examined for abnormal morphology and functional responses. RESULTS: Neutrophils derived from EML-ic/ic cells exhibited nuclear hypolobulation identical to that observed in ichthyosis mice. The ic/ic neutrophils also displayed abnormal chemotaxis, supporting the notion that nuclear segmentation augments neutrophil extravasation. Furthermore, promyelocytic forms of ic/ic cells displayed decreased proliferative responses and produced a deficient respiratory burst upon terminal maturation. CONCLUSIONS: Our studies of promyelocytes that lack LBR expression have identified roles for LBR in regulating not only the morphologic maturation of the neutrophil nucleus, but also proliferative and functional responses that are critical to innate immunity.

Publications

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