Frontline Science: Elevated nuclear lamin A is permissive for granulocyte transendothelial migration but not for motility through collagen I barriers

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Sandeep Kumar Yadav¹  Sara W. Feigelson¹  Francesco Roncato¹  Merav Antman-Passig²  Orit Shefi²  Jan Lammerding³  Ronen Alon¹ 

[1] Department of Immunology, The Weizmann Institute of Science;Faculty of Engineering, Bar Ilan Institute of Nanotechnologies and Advanced Materials, Bar Ilan University;Nancy E. and Peter C. Meinig School of Biomedical Engineering, Weill Institute for Cell and Molecular Biology, Cornell University

关键词: chemokines;    chemotaxis;    granulocytes;    inflammation;    motility;   

DOI  :  10.1002/JLB.3HI1217-488R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Transendothelial migration (TEM) of lymphocytes and neutrophils is associated with the ability of their deformable nuclei to displace endothelial cytoskeletal barriers. Lamin A is a key intermediate filament component of the nuclear lamina that is downregulated during granulopoiesis. When elevated, lamin A restricts nuclear squeezing through rigid confinements. To determine if the low lamin A expression by leukocyte nuclei is critical for their exceptional squeezing ability through endothelial barriers, we overexpressed this protein in granulocyte-like differentiated HL60 cells. A 10-fold higher lamin A expression did not interfere with chemokinetic motility of these granulocytes on immobilized CXCL1. Furthermore, these lamin A high leukocytes exhibited normal chemotaxis toward CXCL1 determined in large pore transwell barriers, but poorly squeezed through 3 ?m pores toward identical CXCL1 gradients. Strikingly, however, these leukocytes successfully completed paracellular TEM across inflamed endothelial monolayers under shear flow, albeit with a small delay in nuclear squeezing into their sub-endothelial pseudopodia. In contrast, CXCR2 mediated granulocyte motility through collagen I barriers was dramatically delayed by lamin A overexpression due to a failure of lamin A high nuclei to translocate into the pseudopodia of the granulocytes. Collectively, our data predict that leukocytes maintain a low lamin A content in their nuclear lamina in order to optimize squeezing through extracellular collagen barriers but can tolerate high lamin A content when crossing the highly adaptable barriers presented by the endothelial cytoskeleton.

【 授权许可】

CC BY