Altered surface expression of effector cell molecules on neutrophils in myelodysplastic syndromes

The surface expression of effector cell molecules on neutrophils was examined in 18 patients with myelodysplastic syndromes (MDS) and 20 healthy control subjects. The MDS patients were further classified as low clinical risk (L-MDS, n  = 7) and high clinical risk (H-MDS, n  = 11). The expression of Fc receptors for IgG (FcR), complement receptors (CR) and cellular adhesion molecules on neutrophils was determined by flow cytometry and monoclonal antibodies. The effect of granulocyte colony-stimulating factor (G-CSF) and tumour necrosis factor-alpha (TNF) on L-selectin shedding and CR up-regulation on neutrophils was also examined. The percentage of FcRI-positive neutrophils and CD11b/CR3 expression on neutrophils were significantly increased in the H-MDS patients when compared to the controls. In contrast, the expression of FcRII, FcRIII, L-selectin, LFA-1 and CD18 on neutrophils was significantly reduced in the H-MDS patients compared with the controls. The L-MDS neutrophils exhibited lower expressions of CR1, L-selectin, LFA-1 and CD18 than those of the controls. Neutrophils from some H-MDS patients showed impaired L-selectin shedding and CR up-regulation after stimulation with G-CSF or TNF, although these were not significantly different when assessed in the whole H-MDS group. These findings suggest that an altered surface expression of effector cell molecules and an impaired modulation of cellular adhesion molecules on neutrophils may contribute to the increased susceptibility to bacterial infections in MDS patients.     

Alterations of effector cell molecule expression on neutrophils in granulocyte colony-stimulating factor-producing tumour

Summary. A 6 8-year-old man was diagnosed as having a granulocyte colony-stimulating factor (G-CSF)-producing mediastinal tumour. Mediastinotomy was performed, and thereafter the elevated leucocyte count and serum G-CSF concentration returned to the normal range. The surface expression of effector cell molecules on neutrophils was serially examined. Before operation, the expression of FcRI and CR1 was increased but the expression of FcRIH and L- selectin was reduced in the patient. The altered expression of these molecules returned to the normal levels after operation. These findings suggest that G-CSF produced by the tumour modulated neutrophil effector cell molecule expression in the patient.     

Granulocyte colony-stimulating factor directly affects human monocytes and modulates cytokine secretion

OBJECTIVE: Recent reports have indicated that monocytes express receptors for the granulocyte colony-stimulating factor (G-CSF). The direct effects of G-CSF on cytokine secretion in monocytes were examined. MATERIALS AND METHODS: A monocytic cell line NOMO-1 that secretes multiple cytokines upon stimulation with lipopolysaccharide (LPS) was used. Normal human monocytes were purified by negative selection using magnetic beads. Cells pretreated with or without G-CSF were stimulated with LPS, and the subsequent concentrations of cytokines and chemokines in supernatants were determined by sandwich enzyme-linked immunosorbent assay. RESULTS: NOMO-1 cells were found to express receptors for G-CSF. Although G-CSF stimulation did not induce cytokine secretion, pretreatment with G-CSF significantly attenuated LPS-stimulated secretion of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin (IL)-12 in NOMO-1 cells. Simultaneously, however, G-CSF pretreatment apparently enhanced LPS-induced secretion of IL-10 and monocyte chemoattractant protein-1, whereas secretions of IL-1beta, IL-6, and IL-8 were unaffected. When normal human monocytes from healthy volunteers were similarly examined, marked individual variations in LPS-induced secretion of cytokines were observed. Although some exceptions exist, a similar tendency as to the effects of G-CSF treatment on cytokine secretions as that in NOMO-1 cells was observed in human monocytes. CONCLUSIONS: Our data suggest that G-CSF directly affects monocytes and modulates their cytokine secretion. NOMO-1 cells can provide an alternate model for in vitro culture of monocytes to investigate the effects of G-CSF on cytokine secretion by these cells.     

Granulocyte colony-stimulating factor and its receptor in acute promyelocytic leukemia

Expression of granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) and in vitro proliferative response to G-CSF were investigated by quantitative immunofluorescence and [³H] thymidine uptake, respectively, in a series of acute myeloid leukemias (AML). The results indicated that G-CSFR was detected at high levels in acute promyelocytic leukemia (APL) cells, in comparison with other types of AML. Moreover, APL cells were also seen to predominantly proliferate in response to G-CSF. Based on these observations, we administered recombinant human G-CSF to a patient with APL in the third relapse that was resistant to both cytotoxic agents and all trans retinoic acid, in an attempt to sensitize the leukemic cells to cell-cycle-dependent agents. Complete remission was achieved. The finding that APL cells are exquisitely responsive to G-CSF supports the view that G-CSF is useful for augmentation of their vulnerability to cell-cycle specific agents. Am. J. Hematol. 58:31–35, 1998. © 1998 Wiley-Liss, Inc.     

Influence of post-transplant recombinant human granulocyte colony-stimulating factor administration on peritransplant morbidity in patients undergoing autologous stem cell transplantation

This study evaluated of the effect of post-transplant recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration on the parameters of peritransplant morbidity. Three sequential and consecutive cohorts of 20 patients each received either post-transplant rhG-CSF at a dose of 5 micro g/kg/d i.v. in the morning, starting on d 0, d 5, or no rhG-CSF. Patients who received rhG-CSF starting on d 0 and 5 recovered granulocytes more rapidly than those not receiving rhG-CSF (P < 0.001 for ANC >or= 0.5 and 1 x 10(9)/l). RhG-CSF administration was not significantly associated with more rapid platelet engraftment. RhG-CSF administration starting on d 0 and 5 was significantly associated with a decreased duration of fever (P = 0.002 and 0.001 respectively), antibiotic administration (P < 0.001 and 0.006 respectively) and shorter hospitalization (P < 0.001 and 0.001 respectively) compared with the reference group. There was no difference between the d 0 and d 5 arms regarding the parameters of peritransplant morbidity. In conclusion, rhG-CSF administration was associated with a faster granulocyte recovery, shorter hospitalization, and shorter period of fever and non-prophylactic antibiotic administration. This study also showed that starting rhG-CSF administration on d 5 may be as effective as d 0 on the clinical outcome and may be an economical approach in routine clinical practice in this cost-conscious era.     

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) secretion by adherent monocytes measured by quantitative immunoassays.

The kinetics of GM-CSF and G-CSF secretion by purified adherent human monocytes were studied by quantitative immunoassays. Interleukin-1 (IL-1); 4-40 ng/ml and E. coli lipopolysaccharide (LPS); 0.1-1.00 ng/ml, were the most effective stimuli and induced dose-dependent secretion of both GM-CSF and G-CSF. Secretion of newly synthesized CSF was detectable 3-6 hours after stimulation and continued for approximately 24 h. Twenty minutes pulse exposure to LPS was sufficient to induce half maximum secretion of GM-CSF, and after 24-36 h the adherent monocytes could not be restimulated. Neither GM-CSF nor TNF could down-regulate the secretion of GM-CSF. IL-3 induced a minor secretion of GM-CSF whereas TNF, G-CSF, M-CSF and IFN-gamma were unable to induce GM-CSF secretion. In addition to LPS and IL-1, GM-CSF and to a minor degree TNF induced G-CSF secretion. Enriched T lymphocytes secreted GM-CSF, but not G-CSF, after stimulation with PHA or staphylococcal enterotoxin A (SEA), whereas LPS and IL-1 were without stimulatory effects. We also noted that enriched T lymphocytes added to LPS-stimulated adherent monocytes at ratios of 1:10 or more inhibited, in a dose-dependent fashion, GM-CSF secretion by 13-55%. These findings add new quantitative data on CSF secretion by human monocytes.     

Granulocyte colony-stimulating factor (rh G-CSF) as an adjunct to interferon alpha therapy of neutropenic patients with hairy cell leukemia

Summary Six patients with hairy cell leukemia (HCL) and neutropenia (median neutrophil count 563/l, range 30–1200) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 5g/kg by daily subcutaneous injection as an adjunct to interferon-alpha (IFN-a) therapy, in order to ameliorate neutropenia. Five of six patients responded to G-CSF with normalization of neutrophil counts (>1800/l) within 2–11 days and a median neutrophil count of 5211/l (range 4312–10160) at the end of G-CSF therapy. In three of these patients, infections resolved when neutropoiesis recovered. In one patient with very severe neutropenia (30/l), in whom myeloid progenitors were not detectable, G-CSF therapy failed to restore granulopoiesis. Cessation or interruption of G-CSF after 2–5 weeks of therapy resulted in a rapid decline of neutrophil counts to lower or subnormal levels (median value 1478/l, range 770–2739) within 1 week, suggesting that the improvement of granulopoiesis was dependent on G-CSF and not due to IFN-a therapy. G-CSF may be a useful adjunct to IFN-a therapy in patients with HCL in order to manage or prevent neutropenic complications in the early phase of treatment.     

Basic fibroblast growth factor modulates the surface expression of effector cell molecules and primes respiratory burst activity in human neutrophils

Basic fibroblast growth factor (b-FGF) mediates a variety of biological responses such as angiogenesis and hematopoiesis. We examined the effect of b-FGF on human neutrophil functions in vitro. The surface expression of effector cell molecules on neutrophils was determined by flow cytometry and monoclonal antibodies. b-FGF increased the expression of CD11b leukocyte integrin and complement receptor type 1 on neutrophils and decreased the expression of L-selectin on neutrophils in a dose- and time-dependent manner. We also examined the effect of b-FGF on the respiratory burst activity in neutrophils. Although b-FGF alone did not induce intracellular oxidative product formation by neutrophils, it enhanced H(2)O(2) production in neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine or phorbol myristate acetate. These findings suggest that b-FGF may participate in the inflammatory process via modulating the surface expression of effector cell molecules and enhancing respiratory burst activity in neutrophils.     

Granulocyte colony-stimulating factor production by human bone marrow fibroblasts stimulated with interleukins

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that mediates the clonal proliferation and differentiation of progenitor cells into mature granulocytes. The kinetics of G-CSF production by human bone marrow fibroblasts (BMF) were investigated by quantitative immunoassays. The spontaneous production of G-CSF by BMF was below the detectable level. Interleukin-1 (IL-1) induced a dose-dependent production of G-CSF, and the production reached a plateau at 50 U/ml of IL-1. G-CSF production by BMF stimulated with IL-1 was cell concentration dependent. Detectable G-CSF was produced by 5 × 10² BMF in a 35 × 10-mm plastic dish. The optimal range was 1 × 10⁴−5 × 10⁴ BMF. Production of newly synthesized G-CSF was detectable 6 hr after stimulation and continued for approximately 48 hr. A 6-hr pulse exposure to IL-1 was necessary to induce production of G-CSF, and after 48 hr, the adherent BMF could not be restimulated. IL-2, IL-3, IL-4, IL-5, and IL-6 were unable to induce G-CSF production. However, IL-4 promoted G-CSF production after stimulation with IL-1. These results provide useful data with regard to the mechanism of G-CSF production by human BMF. © 1996 Wiley-Liss, Inc.     

Effects of granulocyte colony-stimulating factor on neutrophils and inflammatory cytokines in the early stage of severe acute pancreatitis in rats

Background The high mortality rate of severe acute pancreatitis (SAP) is closely associated with secondary infections of pancreatic and peripancreatic tissues. It was reported that granulocyte colony-stimulating factor (G-CSF) increased the number of leukocytes and enhanced their functions. However, an inflammatory response may be enhanced by an increased number of leukocytes. Our purpose was to study the roles of G-CSF in peritoneal-exudate neutrophils and inflammatory cytokines in the early stage of experimental SAP.Methods SAP was induced by injecting 0.2ml of 3% taurocholate acid into the biliopancreatic duct in male Wistar rats. G-CSF (90µg/kg body weight) or saline was administered 1h before the SAP induction. The number of neutrophils and their phagocytic and bactericidal activities were evaluated, and the concentrations of tumor necrosis factor (TNF)-, interleukin (IL)-6, and IL-1 in plasma and ascitic fluid were measured 1h and 3h after the SAP induction.Results The number of peritoneal-exudate neutrophils (PENs) at 3h was increased by G-CSF administration (81 ± 50 × 10⁵ cells/total exudate), as compared with that shown with saline administration (28 ± 13 × 10⁵ cells/total exudate; P < 0.05). The numbers of phagocytic and bactericidal neutrophils were also elevated by G-CSF administration. G-CSF administration did not increase the concentrations of TNF-, IL-6, and IL-1 in the plasma and ascitic fluid.Conclusions G-CSF increases the numbers of neutrophils and enhances their functions against bacteria, but it does not enhance intraabdominal and systemic inflammatory responses in the early stage of SAP.     

Activities of granulocyte-macrophage colony-stimulating factor and interleukin-3 on monocytes

We examined the actions of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) on human monocytes, using a serum-free culture system. GM-CSF and IL-3 did not promote the differentiation of monocytes into macrophages but rather into cells with a phenotype compatible with that of immature dendritic cells (DCs). The addition of fetal bovine serum to serum-free cultures with GM-CSF or IL-3 restored the differentiation of monocytes into macrophages. Cells generated with GM-CSF or IL-3 elicited phagocytic activity. Cells generated in the presence of GM-CSF or IL-3, followed by the addition of tumor necrosis factor-alpha, displayed a phenotype of mature DCs, and primed and stimulated immunogenic peptide-specific T lymphocytes. Surprisingly, GM-CSF and IL-3 inhibited macrophage colony-stimulating factor (M-CSF)-dependent differentiation of monocytes into macrophages and induced differentiation into immature DCs. We asked if the inhibition of M-CSF-dependent differentiation into macrophages by GM-CSF or IL-3 was associated with the expression of M-CSF receptors (M-CSFR). GM-CSF or IL-3 down-regulated the expression of M-CSFR. These data demonstrate that GM-CSF and IL-3 primarily support the differentiation of monocytes into DCs and inhibit M-CSF-dependent differentiation into macrophages by suppressing the expression of M-CSFR, thereby promoting differentiation into DCs.     

Granulocyte colony-stimulating factor (G-CSF) induces the production of cytokines in vivo

Granulocyte colony-stimulating factor (G-CSF) is a haematopoietic growth factor required for the proliferation and differentiation of haematopoietic precursors of neutrophil granulocytes and is now used to overcome congenital and acquired neutropenia. In addition to increasing the numbers of neutrophils in vivo and modulating neutrophil functions, G-CSF may induce the production of cytokines such as tumour necrosis factor alpha (TNF-alpha). In the present study, the plasma levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in six healthy volunteers given G-CSF at 10 microgram/kg once daily for 6 d were measured and found to be elevated. The elevated levels (P < 0.05) were detected on day 2, peaked on days 6-7 and returned to baseline on day 12. In vitro, G-CSF did not enhance the secretion of TNF-alpha and GM-CSF from mononuclear cells, whole blood or endothelial cells. However, in the co-presence of whole blood and endothelial cells, the secretion of TNF-alpha was significantly enhanced by G-CSF at low concentrations. The GM-CSF secretion, however, was unaltered. G-CSF pretreatment of whole blood suppressed lipopolysaccharide (LPS)-induced secretion of TNF-alpha and GM-CSF in a dose-dependent manner. These results together with our previous findings suggest that G-CSF induces the production of TNF-alpha and GM-CSF in vivo, and that this production may be due to the co-effects of endothelial cells and whole blood under the influence of G-CSF through an as yet unknown network of cells and cytokines. Treatment of whole blood with G-CSF suppresses LPS-induced secretion of TNF-alpha and GM-CSF.     

Extramedullary granulopoiesis mimicking recurrent lymphoma after prolonged administration of human recombinant granulocyte colony-stimulating factor

 Human recombinant granulocyte colony-stimulating factor (G-CSF) has become a treatment of choice for neutropenia of diverse etiologies. We describe a 71-year-old man who, while receiving G-CSF for graft failure after peripheral blood stem cell transplant, developed dramatic extramedullary granulopoiesis that mimicked recurrent lymphoma. Received: February 20, 1998 · Accepted: April 15, 1998     

The effect of granulocyte colony-stimulating factor (G-CSF) on the degranulation of secondary granule proteins from human neutrophils in vivo may be indirect

Granulocyte colony-stimulating factor (G-CSF) was administered at a dose of 7.5 or 10 μg/kg s.c. once daily for 6 d (days 1–6) to two groups consisting of eight and six healthy volunteers. The administration of G-CSF resulted in a rapid decrease in neutrophil counts and serum levels of the secondary granule protein, human neutrophil lipocalin (HNL) after 30 min, followed by a recovery and gradual increase within 180 min. The number of circulating neutrophils and plasma and serum levels of neutrophil secondary granule proteins were dramatically elevated on day 2 (1 d after the administration of G-CSF) and stayed so until day 7. The plasma levels of HNL and lactoferrin (LF) showed a biphasic pattern with peaks at day 2 and days 5–7, and remained highly elevated at day 12. The serum levels of HNL and LF increased rapidly (about 8-fold and 6-fold, respectively) on day 2 and stayed elevated until day 7, subsequently returning to baseline levels. At day 5, neutrophil release induced in vitro by f-MLP was significantly enhanced. The cellular contents of HNL and LF were reduced to about 50% of levels before G-CSF administration at day 5. The release of lactoferrin and HNL, but not of myeloperoxidase (MPO), was slightly enhanced after preincubation of isolated normal neutrophils with G-CSF in vitro, but no obvious release of these proteins was observed with G-CSF alone. The administration of G-CSF resulted in a dramatic increase in the alkaline phosphatase (AP) activity in the plasma membrane, with maximal activity occurring at day 5. Furthermore, during administration of G-CSF, TNF-α in plasma increased about 25-fold. TNF-α started to rise at day 2 and peaked at day 6. After discontinuation of G-CSF the levels of TNF-α gradually decreased. The elevated levels of TNF-α (tumour necrosis factor-α) were temporally correlated to the other signs of neutrophil activation. GM-CSF and IL-8, however, were not detected in plasma. Our data suggest that G-CSF affects the neutrophils not only directly but also indirectly by the induction of the production of other cytokines such as TNF-α.     

Expression of HLA-DR, CAM and co-stimulatory molecules on cord blood monocytes

Umbilical cord blood (CB) transplantations are associated with a lower risk of severe graft-versus-host disease (GVHD) compared to BMT. GVHD is an immune reaction that involves interaction between cell surface molecules resulting in cell activation and release of many cytokines. Monocytes are known to be an important source of cell adhesion (CAM) and co-stimulatory molecules which play a crucial role in the efficient activation of T and B cells. We analyzed the phenotype of CB monocytes in the presence or absence of an inflammatory signal (rIFN-gamma) and compared them to adult blood (AB); the expression of HLA-DR and 17 different markers (CD11a, CD11b, CD11c, CD18, CD29, CD40, CD44, CD49a, CD49d, CD49e, CD49f, CD54, CD58, CD62L, CD80, CD86 and CD102) was measured by flow cytometry. Statistical analysis showed that, compared to AB, CB monocytes did not express CD11b, CD11c, CD49d and after stimulation with rIFNgamma, they lost the expression of CD58 and CD102, whereas CD80 and CD86 expression was induced. The analysis of fluorescence intensity (MFI) revealed that CB monocytes expressed some CAM (CD29, CD54, CD102) with a lower intensity than AB monocytes except CD44. In conclusion, absence and reduced expression of some markers argue for a different phenotypic profile of CB monocytes compared to AB monocytes, which might partly contribute to their impaired immune response and to the low incidence of GVHD observed after CB transplantations. However, CB monocytes expressed CD80 and CD86 co-stimulatory molecules, but this expression did not prove a normal co-stimulatory function.     

Induction of tissue factor expression in human monocyte/endothelium cocultures

Summary. Induction of tissue factor (TF) expression on monocyctes and endothelial cells is central to the development of septic coagulopathy. Serum concentrations of endotoxin in septic patients who develop disseminated intravascular coagulation (DIC) do not, however, reach the levels that would directly stimulate TF expression on either monocytes or endothelium. We show, using an in vitro coculture system, that the interaction of monocytes with endothelium induces the expression of significant levels of TF. Unstimulated cocultures of monocytes (2 × 10⁴/well) and endothelial cells (2 × 10⁴/well) produced 35.3± 8.5 mU of PCA/well, representing a 5-fold increase over the combined PCA of each cell type cultured alone (7.1 ± 1.5 mU, n = 6, P < 0.001). Significant enhancement was also found in the presence of low concentrations of LPS. Induction of TF protein was confirmed by Western blotting. Fixation of monocytes with paraformaldehyde completely abolished TF induction in cocultures, whereas fixation of endothelium had no effect, suggesting that TF induction occurred in monocytes rather than endothelial cells. Induction of TF in cocultures could be further augmented by preincubating the endothelial cells with IFN-γ. When endothelium was prestimulated with 500U/ml IFN-γ there was 142 ±11% increase over unstimulated cocultures (n = 5, P< 0.01). TF induction was inhibited by 32 ± 6% in the presence of anti-ICAM-1 mAb (n = 5, P < 001). Our results suggest that monocyte interactions with vascular endothelium, regulated by inflammatory cytokines, and mediated by adhesive ligand binding, leads to the induction of functional monocyte TF protein, which may be responsible for the initiation of DIC in sepsis.     

Granulocyte colony-stimulating factor down-regulates the surface expression of the human leucocyte adhesion molecule-1 on human neutrophils in vitro and in vivo

Summary. The leucocyte adhesion molecule-1 (LAM-1) is the human homologue of the murine peripheral lymph node homing receptor, MEL-14, and might play a crucial role in neutrophil localization at inflammatory sites. We have reported previously that recombinant human granulocyte colony-stimulating factor (rhG-CSF) stimulates or enhances several neutrophil functions in vivo , as well as in vitro. To further explore the possible role of G-CSF in inflammation we studied the effect of rhG-CSF on the surface expression of LAM-1 on human neutrophils, both in vitro and in vivo. The expression of LAM-1 by human neutrophils was investigated by indirect immunofluorescence using flow cytometry and monoclonal antibodies anti-Leu-8 and TQ1. A whole blood analysis was performed to minimize in vitro manipulation. Most circulating human neutrophils expressed LAM-1 on the cell surface. Brief exposure of neutrophils to rhG-CSF in vitro decreased the surface expression of LAM-1. rhG-CSF down-regulated neutrophil LAM-1 expression in a time- and dose-dependent manner. Neutrophils from healthy volunteers and from patients who were receiving rhG-CSF exhibited a decreased expression of LAM-1 after rhG-CSF administration, and the expression thereafter returned or overshot the pretreatment level after stopping rhG-CSF administration. These findings indicate that rhG-CSF down-regulates the surface expression of LAM-1 on human neutrophils in vivo , as well as in vitro , and G-CSF might participate in neutrophil-endothelial cell interaction in inflamed tissue.     

The effect of carotenoids on the expression of cell surface adhesion molecules and binding of monocytes to human aortic endothelial cells

Several large epidemiological studies have shown a correlation between elevated plasma carotenoid levels and decreased risk of cardiovascular disease (CVD). One proposed mechanism for the beneficial effect of carotenoids is through functional modulation of potentially atherogenic processes associated with the vascular endothelium. To test this, we incubated confluent human aortic endothelial cell (HAEC) cultures (passages 4–8) for 24 h with each of the five most prevalent carotenoids in human plasma, which are -carotene, β-carotene, β-cryptoxanthin, lutein, and lycopene, at an approximate concentration of 1 μmol/l. Carotenoids were solubilized in 0.7% (v/v) tetrahydrofuran and incorporated into FBS before adding to cell culture medium. Due to disparate solubilities in aqueous medium, final concentrations of -carotene, β-carotene, β-cryptoxanthin, lutein, and lycopene were 1.7, 1.1, 0.7, 0.9, and 0.3 μmol/l and monolayers accumulated 647, 158, 7, 113, and 9 pmol/mg protein, respectively. Monolayers were then stimulated with IL-1β (5 ng/ml) for 6 h with subsequent determination of cell surface expression of adhesion molecules as measured by an enzyme-linked immunosorbent assay (ELISA). To assess endothelial cell adhesion to monocytes, IL-1β-stimulated monolayers were incubated for 10 min with ⁵¹Cr-labeled U937 monocytic cells and adhesion determined by isotope counting. Pre-incubation of HAEC with β-carotene, lutein and lycopene significantly reduced VCAM-1 expression by 29, 28, and 13%, respectively. Pre-incubation with β-carotene and lutein significantly reduced E-selectin expression by 38 and 34%, respectively. Pre-treatment with β-carotene, lutein and lycopene significantly reduced the expression of ICAM-1 by 11, 14, and 18%, respectively. While other carotenoids were ineffective, lycopene attenuated both IL-1β-stimulated and spontaneous HAEC adhesion to U937 monocytic cells by 20 and 25%, respectively. Thus, among the carotenoids, lycopene appears to be most effective in reducing both HAEC adhesion to monocytes and expression of adhesion molecules on the cell surface.