Gene expression profiles of microvascular endothelial cells after stimuli implicated in the pathogenesis of vasoocclusion.
Altered gene expression in endothelial cells interacting with sickle red blood cells (RBC) and other blood components, in particular the pro-inflammatory cytokines, is an essential step in the pathogenesis of vasoocclusive crises in sickle cell disease (SCD). Using cDNA arrays, we monitored gene expression profiles of human lung microvascular endothelial cells (HMVEC-L) after stimuli that are likely involved in the pathogenesis of vasoocclusion. We detected increased expression of multiple genes in HMVEC-L after their exposure to pro-inflammatory cytokines TNFalpha and IL-1beta and to RBC with increased external exposure of phosphatidylserine and RBC from a patient with SC hemoglobin. While some of these genes have previously been implicated in vascular damage, many represent new targets for investigation of the pathogenesis of vasoocclusion in SCD.
Zachlederova
Marie
M
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Jarolim
Petr
P
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000235:genetics; D018920:Coculture Techniques; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D006451:Hemoglobin, Sickle / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010718:Phosphatidylserines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
C515503:CXCL6 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; D018076:DNA, Complementary; D019040:E-Selectin; D006451:Hemoglobin, Sickle; D007375:Interleukin-1; D015850:Interleukin-6; D010718:Phosphatidylserines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1