Mouse neutrophils lacking lamin B-receptor expression exhibit aberrant development and lack critical functional responses.
OBJECTIVE
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-Huët 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.


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.
Gaines
Peter
P
University of Massachusetts Lowell, Department of Biological Sciences, Lowell, MA 01854, USA. peter_uml.edu
Tien
Chiung W
CW
Olins
Ada L
AL
Olins
Donald E
DE
Shultz
Leonard D
LD
Carney
Lisa
L
Berliner
Nancy
N
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D053144:Cell Nucleus Shape / Q000235:genetics; D002633:Chemotaxis / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D007057:Ichthyosis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D016897:Respiratory Burst / Q000235:genetics*; D000097682:Lamin B Receptor
D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D000097682:Lamin B Receptor; C105949:Pirb protein, mouse