Circulating endothelial cells: A potential parameter of organ damage in sickle cell anemia?

2009 ◽  
Vol 43 (1) ◽  
pp. 63-67 ◽  
Author(s):  
Michiel H. Strijbos ◽  
Precious P. Landburg ◽  
Erfan Nur ◽  
Tom Teerlink ◽  
Frank W.G. Leebeek ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Organ Damage ◽  
Potential Parameter ◽  
Circulating Endothelial Cells

Circulating Endothelial Cells: A Potential Parameter of Organ Damage in Sickle Cell Anemia?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4798-4798
Author(s):  
Michiel Strijbos ◽  
Precious Landburg ◽  
Erfan Nur ◽  
Bart J. Biemond ◽  
Frank Leebeek ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Disease Severity ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Endothelial Activation ◽  
Organ Damage ◽  
Circulating Endothelial Cells ◽  
Laboratory Markers ◽  
Leukocyte Counts ◽  
Painful Crisis

Abstract Traditional laboratory markers of disease severity (Hb concentrations, HbF%, LDH concentrations and leukocyte counts) are not powerful enough to identify individuals with sickle cell disease (SCD) at high risk of complications. In several disease states, the number of circulating endothelial cells (CEC) is indicative of the extent of vascular disease and several small studies employing cumbersome techniques have shown increased CEC to occur in SCD as well. In this pilot study we determined if, by employing the CellSearch system, elevated CEC can be detected in SCD and whether the CEC count is related to the presence of organ damage, painful crisis frequency, traditional laboratory markers of disease severity as well as markers of endothelial activation. Peripheral blood was collected from 15 sickle cell patients and 15 healthy sex, age and race matched HbAA controls. Cells positive for CD146 (present on endothelial cells) are immuno-magnetically isolated and stained with nuclear DAPI and anti-CD105 (present on endothelial cells) and anti-CD45 (pan-leukocyte marker). Within the CD146 enriched cell suspension, cells meeting the DAPI+/CD146+/CD105+/CD45− criteria after image cytometry are designated CEC. CEC counts were significantly higher in sickle cell patients (12 cells/mL, IQR 8–29) as compared to controls (4 cells/mL, 3–10) (p=0.007). CEC counts were significantly higher in patients with pulmonary hypertension (PHT) (p=0.02), and increased with the presence of number of affected organs as well (0–4 involved organs, p=0.03), with the number of affected organs being the most important determinant of increased CEC numbers in SCD (R2=0.72, P=0.001). No statistically significant correlation was detected between CEC counts and markers of endothelial activation (serum sVCAM-1 and plasma VWF:Ag levels). CEC counts did not differ between patients on hydroxyurea and those who did not use hydroxyurea. No statistically significant correlations were detected between CEC counts and painful crisis frequency, Hb, HbF%, leukocyte counts, LDH concentrations. In conclusion, elevated CEC’s can be demonstrated in the clinically asymptomatic state in patients with sickle cell anemia with a validated and automated technique and, for the first time, a relation of CEC counts to SCD related organ damage is demonstrated. Furthermore, the extent of EC activation (as assessed by sVCAM-1 and VWF:Ag levels) is not necessarily related to the extent of EC damage (as assessed by CEC counts).

Sickle Cell Anemia as a Possible State of Enhanced Anti-Apoptotic Tone: Survival Effect of Vascular Endothelial Growth Factor on Circulating and Unanchored Endothelial Cells

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3824-3830 ◽  
Author(s):  
Anna Solovey ◽  
Lizhen Gui ◽  
Sundaram Ramakrishnan ◽  
Martin H. Steinberg ◽  
Robert P. Hebbel
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Circulating Endothelial Cells ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Survival Signals

The biologic processes of apoptosis and angiogenesis are linked in endothelial biology because some endothelial cell growth factors also exert anti-apoptotic effects. We studied whether apoptosis is occurring in circulating endothelial cells (CEC) that have lost the survival signals derived from anchorage to extracellular matrix. Consistent with this expectation, 64% ± 16% of CEC from normal donors showed evidence of apoptosis (by morphology and TdT-mediated dUTP nick end labeling [TUNEL] assay). However, only 30% ± 15% (P < .001 v normal) of CEC from donors with sickle cell anemia were apoptotic. Vascular endothelial growth factor (VEGF) levels were significantly (P = .001) higher in plasma of sickle donors (120.1 ± 81.4 pg/mL) than that of normal donors (37.6 ± 34.6 pg/mL), and there was an inverse correlation between VEGF and CEC apoptosis (r = .612,P = .001). Consistent with stimulation by VEGF, CEC from sickle donors exhibited increased expression of vβ3. In vitro experiments showed that VEGF inhibits apoptosis for cultured endothelial cells that are kept unanchored and not allowed to re-establish attachment to extracellular matrix, thus demonstrating that VEGF provides survival signals independent of its ability to promote matrix reattachment. These data suggest the hypothesis that sickle cell anemia is a state of enhanced anti-apoptotic tone for endothelial cells. If true, this has implications for disease pathobiology, particularly the development of neovascularizing retinopathy.

Sickle Cell Anemia as a Possible State of Enhanced Anti-Apoptotic Tone: Survival Effect of Vascular Endothelial Growth Factor on Circulating and Unanchored Endothelial Cells

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3824-3830 ◽  
Author(s):  
Anna Solovey ◽  
Lizhen Gui ◽  
Sundaram Ramakrishnan ◽  
Martin H. Steinberg ◽  
Robert P. Hebbel
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Circulating Endothelial Cells ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Survival Signals

Abstract The biologic processes of apoptosis and angiogenesis are linked in endothelial biology because some endothelial cell growth factors also exert anti-apoptotic effects. We studied whether apoptosis is occurring in circulating endothelial cells (CEC) that have lost the survival signals derived from anchorage to extracellular matrix. Consistent with this expectation, 64% ± 16% of CEC from normal donors showed evidence of apoptosis (by morphology and TdT-mediated dUTP nick end labeling [TUNEL] assay). However, only 30% ± 15% (P &lt; .001 v normal) of CEC from donors with sickle cell anemia were apoptotic. Vascular endothelial growth factor (VEGF) levels were significantly (P = .001) higher in plasma of sickle donors (120.1 ± 81.4 pg/mL) than that of normal donors (37.6 ± 34.6 pg/mL), and there was an inverse correlation between VEGF and CEC apoptosis (r = .612,P = .001). Consistent with stimulation by VEGF, CEC from sickle donors exhibited increased expression of vβ3. In vitro experiments showed that VEGF inhibits apoptosis for cultured endothelial cells that are kept unanchored and not allowed to re-establish attachment to extracellular matrix, thus demonstrating that VEGF provides survival signals independent of its ability to promote matrix reattachment. These data suggest the hypothesis that sickle cell anemia is a state of enhanced anti-apoptotic tone for endothelial cells. If true, this has implications for disease pathobiology, particularly the development of neovascularizing retinopathy.

scholarly journals Sickle erythrocytes inhibit human endothelial cell DNA synthesis

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 2146-2152 ◽  
Author(s):  
R Weinstein ◽  
MA Zhou ◽  
A Bartlett-Pandite ◽  
K Wenc
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Endothelial Function ◽  
Dna Synthesis ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Inhibitory Effect ◽  
Human Endothelial Cell ◽  
Endothelial Monolayers ◽  
Sickle Erythrocytes

Abstract Patients with sickle cell anemia experience severe vascular occlusive phenomena including acute pain crisis and cerebral infarction. Obstruction occurs at both the microvascular and the arterial level, and the clinical presentation of vascular events is heterogeneous, suggesting a complex etiology. Interaction between sickle erythrocytes and the endothelium may contribute to vascular occlusion due to alteration of endothelial function. To investigate this hypothesis, human vascular endothelial cells were overlaid with sickle or normal erythrocytes and stimulated to synthesize DNA. The erythrocytes were sedimented onto replicate monolayers by centrifugation for 10 minutes at 17 g to insure contact with the endothelial cells. Incorporation of 3H-thymidine into endothelial cell DNA was markedly inhibited during contact with sickle erythrocytes. This inhibitory effect was enhanced more than twofold when autologous sickle plasma was present during endothelial cell labeling. Normal erythrocytes, with or without autologous plasma, had a modest effect on endothelial cell DNA synthesis. When sickle erythrocytes in autologous sickle plasma were applied to endothelial monolayers for 1 minute, 10 minutes, or 1 hour and then removed, subsequent DNA synthesis by the endothelial cells was inhibited by 30% to 40%. Although adherence of sickle erythrocytes to the endothelial monolayers was observed under these experimental conditions, the effect of sickle erythrocytes on endothelial DNA synthesis occurred in the absence of significant adherence. Hence, human endothelial cell DNA synthesis is partially inhibited by contact with sickle erythrocytes. The inhibitory effect of sickle erythrocytes occurs during a brief (1 minute) contact with the endothelial monolayers, and persists for at least 6 hours of 3H-thymidine labeling. These results indicate that interaction between sickle erythrocytes and the endothelium may result in altered endothelial function. This altered endothelial function may contribute to the development of vascular occlusive phenomena in patients with sickle cell anemia.

scholarly journals First report of reversal of organ dysfunction in sickle cell anemia by the use of hydroxyurea: splenic regeneration

Blood ◽  
1996 ◽  
Vol 88 (6) ◽  
pp. 1951-1953 ◽  
Author(s):  
S Claster ◽  
E Vichinsky
Keyword(s):  
Immune System ◽  
Organ Dysfunction ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fetal Hemoglobin ◽  
Organ Damage ◽  
Germinal Centers ◽  
Quadrant Pain ◽  
Significant Impairment ◽  
Splenic Regeneration

Much of the morbidity associated with sickle cell anemia (SCA) is due to ongoing infarction resulting in organ dysfunction. Because the spleen is often the first organ damaged in this illness, there is a significant impairment of the immune system in these patients. Hydroxyurea (HU) has been shown to increase fetal hemoglobin (HbF) and decrease painful episodes in patients with this disease. It is unclear whether HU can prevent organ damage. We treated two SCA patients with HU for several years and found evidence of reversal of previously documented splenic dysfunction. Patient no. 1 was treated for 30 months with an increase in HbF to 30%. HU was stopped because of cytopenia. She developed left upper quadrant pain. A splenectomy was performed due to the possibility of splenic abscesses. A pathologic review found no evidence of infection and an enlarged spleen that showed active germinal centers. Patient no. 2 was treated for 24 months with HU before developing splenomegaly. His HbF levels were 25% to 30%, his pit counts averaged 2%, and his liver spleen scans showed uptake. These two cases show that chronic HU therapy may reverse splenic dysfunction in certain patients and suggest that this drug may have efficacy beyond the elimination of pain in SCA.

scholarly journals Genetic endothelial systems biology of sickle stroke risk

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3872-3879 ◽  
Author(s):  
Liming Chang Milbauer ◽  
Peng Wei ◽  
Judy Enenstein ◽  
Aixiang Jiang ◽  
Cheryl A. Hillery ◽  
...  
Keyword(s):  
At Risk ◽  
Endothelial Cells ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Single Gene ◽  
Vascular Diseases ◽  
Circle Of Willis ◽  
Host Responses ◽  
Genetically Determined ◽  
Not At Risk

Abstract Genetic differences in endothelial biology could underlie development of phenotypic heterogeneity among persons afflicted with vascular diseases. We obtained blood outgrowth endothelial cells from 20 subjects with sickle cell anemia (age, 4-19 years) shown to be either at-risk (n = 11) or not-at-risk (n = 9) for ischemic stroke because of, respectively, having or not having occlusive disease at the circle of Willis. Gene expression profiling identified no significant single gene differences between the 2 groups, as expected. However, analysis of Biological Systems Scores, using gene sets that were predetermined to survey each of 9 biologic systems, showed that only changes in inflammation signaling are characteristic of the at-risk subjects, as supported by multiple statistical approaches. Correspondingly, subsequent biologic testing showed significantly exaggerated RelA activation on the part of blood outgrowth endothelial cells from the at-risk subjects in response to stimulation with interleukin-1β/tumor necrosis factorα. We conclude that the pathobiology of circle of Willis disease in the child with sickle cell anemia predominantly involves inflammation biology, which could reflect differences in genetically determined endothelial biology that account for differing host responses to inflammation.

Evaluation of Splenic Function in Infants with Sickle Cell Anemia in the BABY HUG Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3587-3587
Author(s):  
Zora R. Rogers ◽  
Renee R. Rees ◽  
Winfred C. Wang ◽  
Daner Li ◽  
Rathi V. Iyer ◽  
...  
Keyword(s):  
Young Children ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Geometric Mean ◽  
Organ Damage ◽  
Phase Iii ◽  
Qualitative Assessment ◽  
Splenic Function ◽  
Clinical Complications ◽  
Normal Mean

Abstract Organ damage in children with sickle cell anemia [SCA] begins with the spleen. Hydroxyurea [HU] decreases clinical complications and mortality in severely affected adults with SCA, and has proven hematologic benefits in children. To critically assess the efficacy of HU in preventing chronic organ damage, the Pediatric Hydroxyurea Phase III Clinical Trial [BABY HUG], an NHLBI sponsored double-blinded placebo-controlled multi-center trial, was initiated. One objective of the Feasibility and Safety Pilot is to evaluate novel strategies for assessment of splenic function in young children with SCA. To date 23 subjects (13 male; median age 12.9 mos, range 10.3–17.6 mos) have been recruited without regard to disease severity. Pretreatment spleen function determined by Tc-99m sulfur colloid liver-spleen [LS] scan was compared to pocked erythrocyte [PIT] counts and flow cytometric quantitation of Howell-Jolly Bodies [HJB]. Results were correlated with total [Hgb] and % fetal [HbF] hemoglobin, white blood cell [WBC] and platelet [PLT] counts. Splenic uptake of Tc-99m was qualitatively graded as normal, decreased, or absent by two nuclear medicine physicians. Of 17 LS scans reviewed 3 had normal (mean age 12.2 mos) and 14 decreased (mean age 14.6 mos) spleen function. LS scans were also imaged quantitatively by determining the geometric mean total counts over the spleen. Although there was a trend for qualitative LS scan results to discriminate splenic function among patients (p=.08), quantitative spleen counts demonstrated a stronger relationship between lower uptake and reduced splenic function. A logarithmic transformation was applied to each measure (except age) to improve linearity with other variables and stabilize the variance of the transformed data. PIT counts (p<.0001) and WBC counts (p=.023) were significantly linearly associated with age. Age was inversely related to Hgb (p=.005) and %HbF (p=.009), but not associated with PLT (p=.54) or HJB (p=.38). Quantitative spleen counts were related inversely to age (p<.01), PIT counts (p=.02), and WBC (p=.026); linearly to %HbF (p=.0003) and Hgb (p=.04); and had no relationship with HJB (p=.39) or PLT (p=.68). In multivariate analysis with age and PIT counts, the decline in spleen counts had the strongest association with %HbF (p=.006). A PIT count of 3.5%, which classically divides normal from decreased spleen function, separated spleen counts into significantly different groups (p<.001). No similar relationship existed for HbF 25% (p=.059), Hgb 8 g/dl (p=.15), or HJB 300/million rbc (p=.28). These preliminary data indicate that the decline of splenic function with age in young children with SCA can be effectively assessed by multiple techniques in a multi-center study. Compared to the traditional qualitative assessment, quantitative evaluation of the LS scan will allow more informative gradation of the decline in splenic function for the BABY HUG study. Surrogate measures such as PIT counts and %HbF are associated with LS scan results, and may prove to be informative non-invasive markers predictive of splenic function.

Vascular Consequences of Cocaine Exposure.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3718-3718
Author(s):  
William E. Hobbs ◽  
Chen Jun-Mei ◽  
López A. José
Keyword(s):  
Endothelial Cells ◽  
Platelet Activation ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Vascular Endothelium ◽  
Whole Blood ◽  
Fold Increase ◽  
Dependent Manner ◽  
Cocaine Exposure ◽  
Cocaine Use

Abstract Cocaine use is associated with sudden cardiac death, cardiac ischemia, and stroke in patients with no additional risk factors and is a frequent cause of these syndromes in patients with sickle cell disease. Pathologic findings include platelet-rich microthrombi and an increased plasma concentration of von Willebrand Factor (VWF). These findings suggest that, in addition to the well-known cocaine effects of vasoconstriction and increased tissue oxygen demand, activation of platelets and/or endothelial cells contributes to cocaine-induced ischemia. However, studies investigating the effect of cocaine on platelet functions have been inconclusive, finding both platelet activation and inhibition depending on the assay used. Further, the ability of cocaine to activate the vascular endothelium has not been examined, in particular, the endothelial secretion of the most adhesive forms of VWF, the ultralarge forms (ULVWF). ULVWF are long VWF multimers that remain tethered to the endothelial surface upon secretion, extend into the blood vessel lumen under laminar flow in long strings measuring up to 0.5 cm in length, and have multiple exposed binding sites for receptors on platelets, erythrocytes, and leukocytes. Elevated levels of ULVWF, due either to enhanced secretion or defective processing, have been implicated in diseases such as thrombotic thrombocytopenic purpura (TTP) and sickle cell anemia. We hypothesized that a major consequence of cocaine exposure is activation of the vascular endothelium to secrete ULVWF, which would provide a platform for blood cell adhesion and subsequent thrombosis or vaso-occlusion. We evaluated the ability of cocaine to stimulate ULVWF from cultured endothelial cells in a parallel-plate flow chamber assay and found that 1 μg/ml cocaine, a level comparable to peak blood levels detectable in cocaine abusers, efficiently induced secretion of ULVWF capable of binding platelets under flow conditions similar to that induced by histamine 6 μg/ml (3.92 ULVWF strings/field with cocaine vs. 4.62 strings/field with histamine). We also assessed the activation of platelets exposed in vitro to cocaine by flow cytometry, using two markers of platelet activation: P-selectin expression (which signals a-granule release) and conformational activation of the platelet integrin aIIbb3, detected with the antibody PAC-1. We found that when platelet-rich plasma was incubated with cocaine at concentrations from 0.1 μg/ml to 10 μg/ml, there was no increase in P- selectin exposure or PAC-1 binding. Furthermore, pretreatment of platelets with cocaine inhibited the ability of platelets to subsequently be activated by ADP in a dose-dependent manner. We did not observe any increase in mean fluorescence above background in ADP stimulated platelets pre-incubated with 1 μg/ml cocaine for P-selectin or PAC-1 binding. However, exposure of platelets in whole blood to 1 μg/ml cocaine resulted in a 3.2-fold increase in P- selectin exposure and a 5.4-fold increase in PAC-1 binding. These results indicate that cocaine directly activates the vascular endothelium to secrete ULVWF, and activates platelets indirectly, involving as yet unknown factors in whole blood, resulting in the formation of microthrombi. These effects of cocaine are likely to have pathogenic roles in cardiovascular syndromes associated with cocaine use, including the triggering of vaso-occlusive crises in sickle cell anemia and may explain the observed association of cocaine use with TTP.

Increased Platelet-Derived CD40L May Modulate Endothelial Cell ICAM-1 Expression and Interact With Leukocytes In Sickle Cell Anemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 974-974
Author(s):  
Vanessa Tonin Garrido ◽  
Renata Proença-Ferreira ◽  
Venina M. Dominical ◽  
Marcos André Cavalcanti Bezerra ◽  
Aderson S. Araujo ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Endothelial Cells ◽  
Steady State ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Repeated Measures ◽  
Conflicts Of Interest ◽  
Endothelial Activation ◽  
Surface Expression ◽  
Platelet Surface

Abstract Background Vaso-occlusive events are a major cause of morbidity in sickle cell anemia (SCA) and attributable to the abnormal adhesion of red cells and leukocytes to the endothelium. Platelets may contribute to the chronic inflammation and endothelial activation that initiates the vaso-occlusive process. We hypothesized that platelet-associated CD40 ligand (CD40L) may contribute to platelet-mediated inflammatory responses in SCA. Aims This study evaluated the platelet (PLT) release of CD40L, the expression of its receptor (CD40) on platelets, neutrophils, lymphocytes and monocytes of control individuals (CON) and SCA patients, and also the ability of platelet-derived CD40L to activate endothelial cells. Methods IL-8, soluble ICAM-1, VCAM-1 and CD40L were determined in PLT-free plasma or the supernatant of stimulated (ADP or Collagen) and unstimulated PLTs (2•10⁸/mL in Kreb’s buffer), from CON individuals and steady-state SCA patients, by ELISA. Flow cytometry was used to analyze CD40 expression on platelets, neutrophils, lymphocytes and monocytes from the peripheral blood of the study’s subjects. Human umbilical vein endothelial cells (HUVECs) were cultured (1x106cells/well; 37°C, 5% CO2) together with PLTs (3x108PLTs/well) from CON individuals or steady-state SCA patients for 24h, 37°C, 5%CO2, in the presence, or not, of blocking antibodies against CD40L. After incubation, PLTs were removed and HUVECs analyzed by flow cytometry for CD54 (ICAM-1) surface expression. Results SCA individuals presented elevated levels of plasma CD40L (724.4± 55.7 pg/ml; n=90) compared to CON (241.5±34.6 pg/ml; n=41; P<0.0001) and these levels correlated with PLT counts (rs=0.255; P=0.015). No correlation was found between plasma CD40L and plasma IL-8, ICAM-1 or VCAM-1. PLT release of CD40L (90 min, 37°C, 5%CO2) was evaluated; PLTs of SCA patients released higher quantities of CD40L (8347±1464 pg/108 PLTs; n=10) than PLTs of CON individuals (3652±568 pg/108 PLTs; n=5; P=0.019). CD40L release from SCA PLTs was augmented by incubation with collagen (P<0.001), but not ADP. Expression of the CD40 receptor on the platelet surface was elevated in the SCA group (52.4±2.7% positive cells; n=23), compared to the CON group (36.8±3.7% positive cells; n=9; P=0.005). The surface expression of CD40 was also elevated on neutrophils (SCA, 10.4±1.5% positive cells, n=14; CON, 5.5±1.1% positive cells, n=13; P=0.03), lymphocytes (SCA, 8.3±0.8% positive cells, n=16; CON, 3.6±0.4% positive cells, n=14; P<0.001) and monocytes (SCA 69.6±5.9% positive cells, n=16; CON, 49.9±5.8% positive cells, n=14; P=0.03) of SCA patients, compared to controls. ICAM-1 expression on the surface of HUVECs (Basal expression 32.8±1.8%, n=11) was significantly increased following incubation with SCA PLTs (54.0±4.8%, n=11, p<0.0001) and slightly augmented after incubation with CON PLTs (40.8±3.1%, n=11, p<0.05; Repeated measures ANOVA). Interestingly, when HUVECs and SCA PLTs were incubated with a blocking antibody against CD40L, the increase in ICAM-1 expression was significantly reversed on HUVECs (HUVECs, 28.1±0.2%, n=6; HUVECs+SCA PLTs, 42.0±3.3%, n=6; HUVECs+SCA PLTs+anti-CD40L 28.9±1.5%, n=6; P<0.01). Conclusions Plasma levels and platelet release of CD40L were found to be significantly elevated in SCA, in association with increased expressions of the CD40 receptor on SCA PLTs, neutrophils, lymphocytes and monocytes, possibly indicating a CD40L-mediated crosstalk between platelets and leukocytes in SCA. Platelets from SCA patients can induce adhesion molecule expression on the surface of endothelial cells in vitro, and this up-regulation may be modulated by platelet-derived CD40L. Results suggest that the CD40/CD40L pathway may be altered in SCA and that platelets may participate in this up-regulation. Given the potent inflammatory effect of this cytokine, a role for platelets and this cytokine in endothelial activation, inflammation and consequent vaso-occlusion, is likely. Disclosures: No relevant conflicts of interest to declare.

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