A novel role for PECAM-1 (CD31) in regulating haematopoietic progenitor cell compartmentalization between the peripheral blood and bone marrow.
Although the expression of PECAM-1 (CD31) on vascular and haematopoietic cells within the bone marrow microenvironment has been recognized for some time, its physiological role within this niche remains unexplored. In this study we show that PECAM-1 influences steady state hematopoietic stem cell (HSC) progenitor numbers in the peripheral blood but not the bone marrow compartment. PECAM-1(-/-) mice have higher levels of HSC progenitors in the blood compared to their littermate controls. We show that PECAM-1 is required on both progenitors and bone marrow vascular cells in order for efficient transition between the blood and bone marrow to occur. We have identified key roles for PECAM-1 in both the regulation of HSC migration to the chemokine CXCL12, as well as maintaining levels of the matrix degrading enzyme MMP-9 in the bone marrow vascular niche. Using intravital microscopy and adoptive transfer of either wild type (WT) or PECAM-1(-/-) bone marrow precursors, we demonstrate that the increase in HSC progenitors in the blood is due in part to a reduced ability to migrate from blood to the bone marrow vascular niche. These findings suggest a novel role for PECAM-1 as a regulator of resting homeostatic progenitor cell numbers in the blood.
Rheumatology Research Group, MRC Centre for Immune Regulation, University of Birmingham, Birminham, United Kingdom.
Ewan A
EA
Ross
Sylvie
S
Freeman
Yan
Y
Zhao
Tarvinder S
TS
Dhanjal
Emma J
EJ
Ross
Sian
S
Lax
Zubair
Z
Ahmed
Tie Zheng
TZ
Hou
Neena
N
Kalia
Stuart
S
Egginton
Gerard
G
Nash
Steve P
SP
Watson
Jon
J
Frampton
Christopher D
CD
Buckley
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002451:Cell Compartmentation / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology*
D054377:Chemokine CXCL12; D019408:Platelet Endothelial Cell Adhesion Molecule-1