Reduced number and impaired function of circulating progenitor cells in patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is associated with premature and accelerated atherosclerosis. Circulating progenitor cells (CPCs) are circulating bone-marrow derived cells that play an important role in the repair of vascular damage that underlies the development of atherosclerosis. The objective of this study was to determine the number and functionality of CPCs in patients with SLE. The study included 44 female SLE patients in an inactive stage of disease and 35 age-matched female controls. CPC numbers in the circulation were determined by FACS with monoclonals against CD14, CD34 and CD133. Peripheral blood-derived mononuclear cell (PBMNC) fractions were cultured in angiogenic medium. The endothelial-like phenotype was confirmed and the colony forming unit (CFU) capacity, migratory capacity and the potential to form clusters on Matrigel were determined. Expression of apoptosis inhibiting caspase 8L was analyzed in PBMNCs and CPCs by gene transcript and protein expression assays. The number of CD34-CD133 double-positive cells (P < 0.001) as well as the CFU capacity (P = 0.048) was reduced in SLE patients. Migratory activity on tumor necrosis factor-alpha tended to be reduced in patient CPCs (P = 0.08). Migration on vascular endothelial growth factor showed no significant differences, nor were differences observed in the potential to form clusters on Matrigel. The expression of caspase 8L was reduced at the transcriptional level (P = 0.049) and strongly increased at the protein level after culture (P = 0.003). We conclude that CPC numbers are reduced in SLE patients and functionality is partly impaired. We suggest these findings reflect increased susceptibility to apoptosis of CPCs from SLE patients.
Moonen
Jan Renier A J
JR
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, The Netherlands. j.a.j.moonen@med.umcg.nl
de Leeuw
Karina
K
van Seijen
Xavier J Gallego Y
XJ
Kallenberg
Cees G M
CG
van Luyn
Marja J A
MJ
Bijl
Marc
M
Harmsen
Martin C
MC
D000328:Adult; D017209:Apoptosis; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D003114:Colony-Forming Units Assay; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index
D012333:RNA, Messenger; C505530:CASP8 protein, human; D053181:Caspase 8