We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Elevated plasma levels and platelet-associated expression of the pro-thrombotic and pro-inflammatory protein, TNFSF14 (LIGHT), in sickle cell disease.
- Authors
Garrido, Vanessa T.; Proença-Ferreira, Renata; Dominical, Venina M.; Traina, Fabiola; Bezerra, Marcos A. C.; Mello, Mariana R. B.; Colella, Marina P.; Araújo, Aderson S.; Saad, Sara T. O.; Costa, Fernando F.; Conran, Nicola
- Abstract
Chronic vascular inflammation and endothelial activation may initiate vaso-occlusion in sickle cell disease ( SCD). TNFSF14 ( CD258; LIGHT), a recently-identified pro-thrombotic and pro-inflammatory tumour necrosis factor ( TNF)-superfamily cytokine, has a potent activating effect on endothelial cells. We evaluated whether TNFSF14 production is altered in SCD and whether platelets contribute to this production. TNFSF14 was measured in platelet-free plasma from healthy-control individuals ( CON), steady-state sickle cell anaemia ( SCA), SCA on hydroxycarbamide therapy ( SCAHC) and haemoglobin SC (Hb SC) patients. Mean plasma TNFSF14 was significantly increased in SCA, SCAHC and Hb SC, compared to CON individuals. In SCA/ SCAHC patients, plasma TNFSF14, showed no correlation with haematological variables, but was significantly correlated with serum lactate dehydrogenase and inflammatory markers ( CD40 LG , IL8 and ICAM1). Platelet-membrane TNFSF14 expression was significantly augmented on SCA platelets, and correlated with platelet activation; furthermore, measurement of platelet TNFSF14 release indicated that platelets may be a major source of circulating TNFSF14 in SCA. Interestingly, high plasma TNFSF14 was significantly associated with elevated tricuspid regurgitant velocity (≥2·5 m/s) in a population of SCA/ SCAHC patients. The pro-inflammatory and atherogenic cytokine, TNFSF14, could contribute to endothelial activation and inflammation in SCA; future investigations may confirm whether this protein contributes to major clinical complications of the disease, such as pulmonary hypertension, and represents a potential therapeutic target.
- Subjects
SICKLE cell anemia; BLOOD plasma; VASCULITIS; TUMOR necrosis factors; BLOOD platelets; THROMBOSIS; VASCULAR endothelium
- Publication
British Journal of Haematology, 2012, Vol 158, Issue 6, p788
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/j.1365-2141.2012.09218.x