However, the

role of innate immunity in diabetic nephropathy (DN) has yet to be demonstrated. The aim of this study was to investigate the expression of toll-like receptors (TLR) and its ligands in human kidney tissue of DN. Methods: We studied 12 type 2 DN patients with renal biopsy, and 12 patients with nephrectomy for renal cancer served as controls. Clinical characteristics were recorded, and intrarenal expression of TLRs (TLR2 and TLR4) and its ligands (heat shock protein70, HSP70 and MYD88) was examined by immunohistochemistry. Results: The intrarenal expression of TLR2 was markedly decreased in glomerulus of the DN group (1.30 ± 0.21%/mm2 vs. 28.50 ± 3.45%/mm2, P < 0.01), whereas its expression was increased in the tubulointerstitum (16.55 ± 0.75%/mm2 vs. 8.93 ± 0.62%/mm2, P < 0.05), and this trend was accompanied by MYD88 expression (Glomerulus:

1.76 ± 0.60%/mm2 Luminespib supplier https://www.selleckchem.com/products/Imatinib-Mesylate.html vs. 90.92 ± 10.69%/mm2; tubulointerstitum: 24.48 ± 2.38%/mm2 vs. 16.15 ± 1.12%/mm2, P < 0.01, respectively). In contrast, TLR4 immunoreactivity was significantly increased in the glomerulus of DN group (45.65 ± 3.08%/mm2 vs. 31.61 ± 1.32%/mm2, P < 0.01) but not in the tubulointerstitum. HSP70 expression, a TLR ligand, was significantly increased in the DN group compared with the Con group (Glomerulus: 91.40 ± 13.88%/mm2 vs. 50.91 ± 4.07%/mm2; tubulointerstitum: 19.27 ± 1.23%/mm2 vs. 9.25 ± 0.74%/mm2, P < 0.01, respectively). Correlation Carbohydrate analysis revealed that TLRs expression was correlated with the proteinuria and the eGFR. Conclusion: These findings suggest that an alteration in TLRs and its ligands expression is closely associated with diabetic renal injury, and that innate immunity may be one of important

players in type 2 DN. FUJITA TAKAYUKI1, WATANABE HIDETSUNA WATANABE2, HEMMI SEIICHIRO1, YABUKI MINAKO1, FUKE YOSHINOBU1, SATOMURA ATAUSHI3, SOMA MASAYOSHI1,4 1Department of Nephrology, Hypertension and Endocrinology, Nihon University School of Medicine; 2Department of Internal Medicine, Sakuboukai Tokiwadaigeka Hospital, Tokyo, Japan; 3Department of Laboratory Medicine, Nihon University School of Medicine, Tokyo, Japan; 4Department of General Medicine, Nihon University School of Medicine, Tokyo, Japan Introduction: Glomerular endothelial injury is commonly encountered in diabetic nephropathy, as in type 2 diabetes mellitus (T2DM). Microalbuminuria is associated with endothelial cell dysfunction, and is a significant risk factor for cardiovascular mortality in diabetes. This study was undertaken to study the effect of sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, on microalbuminuria as a mechanism of improving glomerular endothelial injury in patients with T2DM. Methods: Sitagliptin, a DPP4 inhibitor, was administered to twenty patients with T2DM, 50 mg/day, for 8 weeks.

There was no significant difference between the three infection

groups in lymphocyte, monocyte, basophil or neutrophil counts. It has been shown that glycosylated components of 0–3 h RP have an important role for inflammatory cytokine production by murine macrophages [8, 9] and polarization of the acquired immune response after infection [9]. Here, we investigate the influence of glycans in 0–3 h RP on human cytokine responses to cercarial E/S material in schistosome-infected participants. Consequently, aliquots of total 0–3 h RP were treated with sodium meta-periodate (smp0–3 h RP) to disrupt glycan residues or ‘mock-treated’ (m0–3 h RP) as the control. This investigation was conducted in www.selleckchem.com/products/FK-506-(Tacrolimus).html 26 participants for whom there was sufficient blood sample volume to conduct the additional WB cultures (infected n = 11, co-infected n = 15). Using paired WB cultures for these individuals, periodate treatment of 0–3 h RP significantly

Selleck PCI 32765 reduced production of IL-8 (Z: −2·354, P = 0·019), TNFα (Z: −4·178, P < 0·001) and IL-10 (Z: −2·134, P = 0·033) when compared with that produced in response to the mock-treated 0–3 h RP (Figure 4). The ratio of IL-10: TNFα did not differ significantly between periodate-treated and mock-treated control cultures (Z: −0·711, P = 0·477). Furthermore, there was no significant difference between the infected and co-infected groups in the fold change in cytokine secretion between cultures stimulated with m0–3 h RP and smp0–3 h RP (TNFα Z: −0·176, P = 0·861, Epothilone B (EPO906, Patupilone) IL-8 Z: -0·333, P = 0·739, IL-10 Z: −1·094, P = 0·274). In schistosomiasis, cercarial E/S molecules are the

first molecules to be presented at the interface with the host’s immune system and are liable to be major agents in stimulating or modulating the innate immune response in the skin [5, 27]. This is particularly relevant given repeated exposure to cercariae is likely to occur in areas endemic for schistosomiasis. However, it is not known to how many cercariae and on how many occasions any particular individual has been exposed. It is also not known how the innate and acquired immune response in infected humans is affected by such repeated exposure. We have, however, recently shown that cercarial E/S products are major stimulants of murine innate immune cells including dendritic cells and macrophages [4, 8, 9, 25] and that multiple infection of mice with cercariae induces myeloid cells with an ‘alternately-activated’ phenotype, which down-modulate pathological immune responses to schistosome eggs in the liver [10]. Now, we extend studies on cercarial E/S products to the innate/early cytokine response in the natural human host in a schistosome-endemic region.

The aim of this study is to evaluate the association of the course of depression symptoms, based on repeated assessments of depression symptoms over time, with left

ventricular mass index (LVMI) and left ventricular filling pressure (LVFP) in patients on haemodialysis (HD). Methods:  The level of depression symptoms in 61 patients on HD were prospectively assessed using the Beck Depression Inventory (BDI) at baseline and at three intervals (5, 10, 15 months). Doppler echocardiographic examinations were performed at the end of follow up. Results:  At the end of follow up, the patients were divided into three groups according to their course of depression symptoms: non-depression click here (n = 21), intermittent depression (n = 23) and persistent depression (n = 17). LVMI and LVFP were significantly increased in the persistent depression symptoms group compared to those of the non-depression symptoms group and the intermittent depression symptoms group. Persistent depression symptoms were independently associated with LVMI (β-coefficient = 0.347, P = 0.017)

and LVFP (β-coefficient = 0.274, P = 0.048) after adjustment for age, sex, systolic blood pressure, diastolic blood pressure, diabetes and interdialytic weight gain. Conclusion:  In our study, persistent depression symptoms were associated with left ventricular hypertrophy and diastolic dysfunction. Our data may provide a more complete understanding of cardiovascular risk associated with depression symptoms in patients learn more on HD. “
“Aim:  The role of the tumour necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 and interferon-inducible protein (IP-10)/CXCR3 axis in the pathogenesis of lupus nephritis were studied. Methods:  The mRNA expression of TWEAK, Fn14, IP-10 and CXCR3 were quantified in the glomerulus and tubulointerstitium of 42 patients with lupus nephritis (LN group) and 10 healthy controls.

Results:  As compared to controls, LN patients had higher glomerular expression of TWEAK and Fn14, but glomerular CXCR3 expression was lower in the LN group. Similarly, the LN group had higher tubulointerstitial expression of TWEAK and Fn14, but lower tubulointerstitial expression of CXCR3, than controls. Glomerular TWEAK expression Temsirolimus cost of class V nephritis was significantly higher than class IV nephritis. Glomerular expression of CXCR3 significantly correlated with proteinuria (r = −0.532; P = 0.019), whereas tubulointerstitial CXCR3 significantly correlated with serum creatinine (r = −0.447; P = 0.029). Conclusion:  In patients with lupus nephritis, there is an increase in intra-renal expression of TWEAK and Fn14, and a decrease in CXCR3 expression. Intra-renal expression of CXCR3 correlates with proteinuria and renal function. Our findings suggest that the TWEAK/Fn14 and IP-10/CXCR3 axis may contribute to the pathogenesis of lupus nephritis.

The different concentrations we chose KPT-330 nmr to test were derived from previous publications on the subject. In in vitro studies, the average concentration of CsA leading to observable positive effects in cellular bath solution is 1 μM [15, 20, 30]. Higher concentrations (10 and 30 μM) were chosen from previous in vivo publications reporting blood concentrations of CsA between 1 and 5 μM in humans [8, 47], and up to 90 μM in rats [26].

In our data, CsA has shown to be deleterious on pressures and resistances, with a dose-dependent effect. Although daily administrations of CsA for three weeks seemed to prevent pulmonary hypertension induced by chronic hypoxia [24], several studies showed that CsA could be responsible for hypertension in humans after lung, heart, kidney, or liver transplantations [16, 29, 38, 49]. Two stages were described, the first,

which was acute hypertension during initiation of CsA treatment, selleck chemicals and second, a chronic hypertension after long-term administration. CsA binds to Cyclophilin-A (an immunophilins cytoplasmic receptor) in smooth vascular muscles and may directly affect blood pressure regulation by reducing the endothelial production of nitric oxide by NO synthase [37]. This mechanism could account for the increase in PAP, Pcap, and PVR we observed in our lungs treated with CsA, especially those receiving higher doses (10 and 30 μM). It has been studied that IRI induces a hypoxic mediator-induced active vasoconstriction, which results in a perivascular compression by edema, and an intravascular obstruction by thromboembolism or endothelial swelling [13]. The active reversible vasoconstriction accounts for approximately fifty percent of the hypoxic pulmonary hypertension. Endothelial cell exposure to CsA generates reactive oxygen and nitrogen species [35] that may

enhance this pulmonary vasoconstriction. These early hemodynamic effects may be synergic with intrinsic cellular properties Sirolimus supplier of CsA against IRI. However, beyond a certain level of CsA (over 10 μM in our experiment), vasoconstriction and blood flow redistribution may aggravate the injury by an over-perfusion of mildly injured zones. Increasing blood flow and PAP to lesser damaged and equally injured zones can allow for major fluid filtration through the capillary-alveolar membrane as described by the Starling equation [42]. Over-perfusion could have re-opened non-flowing leaky capillaries in zone 1, called “blind capillaries” (i.e., open at their arterial end and obstructed at their venous end) and shifted the obstruction point downstream under zone 2 conditions toward the venous ends of the capillaries and veinules. These microvascular mechanisms have been described in other models of isolated lung injury [2, 6], which were consistent with an increase of the post-capillary (i.e., veinular) part of the PVR observed in our experiments with high doses of CsA.

L. mexicana-infected cells display activation of PKCα (Figure 2b), which is confirmed by purified LPG incubated with PKCα (Figure 2a). LPG activation of PKCα then leads to enhanced oxidative burst (Figure 3a), thus reducing parasite survival, as compared with nonstimulated controls (Figure 4). It is noteworthy, that in contrast to

purified LPG, the complete parasite inhibits the respiratory burst in C57BL/6 macrophages, albeit to a lesser degree than observed for BALB/c cells. This inhibitory response in the oxidative burst induced by the whole parasite could be related to a variety of other molecules and mechanisms in addition to LPG, such as the possible recognition of opsonized parasites by CR3, a complement receptor that inhibits the oxidative burst (43). The importance of PKCα in parasite control is further strengthened by the fact that Buparlisib clinical trial the PKCα inhibitor Gö6976, which significantly reduced the oxidative burst in macrophages of both mouse strains, allowed an enhanced parasite survival in macrophages not only in BALB/c cells but also in C57BL/6 cells, which

were originally able to limit parasite survival. These data underscore the importance of the varying modulation of PKCα by L. mexicana LPG in regulating parasite survival within macrophages. Epacadostat The opposing response of macrophages from both mouse strains seems to be specifically related to L. mexicana LPG and not to alterations in the PKCα enzyme, as a nonspecific stimulus, such as PMA, modified the enzymatic activity of PKCα in an identical manner in macrophages of both mouse strains. The opposing effect of LPG on PKCα of both mouse strains is noteworthy, as to date, it has only been reported that L. donovani LPG inhibits about PKC isolated from rat brain.

In that study, it was shown that LPG is a competitive inhibitor of diolein on the regulatory binding site C1 of PKC (44). Although the LPG binding site on PKCα has not been mapped, results suggest that LPG must bind to C1 region of PKC. Comparison of the primary sequence of PKCα C1 site between the two mice strains used in our study (data not shown) showed no differences between them. As post-translational modification represents a ubiquitous and essential device for control of PKC activity, localization, stability and protein–protein interaction, it would be possible that the opposite effect exhibited by LPG may be as a result of differences in post-translational modifications found in PKCα at or near this site en each mouse strain (45). In addition, it has been proposed that differences in specificities of high and low affinity phorbol ester-binding sites may partially contribute to distinct effects on PKC-regulated cellular processes (46).

These data were similar to Polchert et al. and Joo et al., where murine MSC therapy significantly improved the histological score of the intestine

and liver of mice with GVHD [32, 42]. Unlike Polchert et al., human MSC therapy did not improve the histological analysis of the lung in NSG mice with aGVHD, as there was a significant amount of cell infiltration in all treatment groups (Fig. 2). Importantly, the histological selleck chemicals llc results herein mirrored those of a recent Phase III human clinical trial [27]. This trial set out to examine the effects of human MSC, Prochymal®, in the treatment of patients with steroid-refractory aGVHD. Although Prochymal® cell therapy was well tolerated in patients with no adverse effects in a Phase II trial [25], findings of a Phase III trial have been difficult to interpret mechanistically. In the Phase III clinical trial, patients who presented with aGVHD manifesting in the liver and the gut showed significant improvement following treatment,

similar to that seen here. However, cell therapy had no beneficial effect on skin manifestations. Although histological analysis of the skin was not examined in the humanized model, the beneficial effect of MSC-based cell therapy here was also target organ-dependent. This might be linked to MSC localization to different target organs, a hypothesis testable in the model we describe. The major benefit of this model is that it allows a mechanistic selleck compound exploration of MSC therapy not possible in patients, and specifically the link between MSC therapy and immunological tolerance. The induction of immune tolerance involves a precise balance between activation and inhibition of T cell responses, which is important in the development of GVHD.

Tolerance can occur through the induction of lymphocyte apoptosis, anergy, regulatory cell induction/expansion or the direct inhibition of lymphocyte proliferation. Several studies have given contradictory evidence in relation to the induction of T cell apoptosis by MSC [46, 47]. In this study, MSC did not induce apoptosis of PBMC in vitro (Fig. 4) or suppress engraftment Progesterone (Fig. 3). MSCγ therapy to NSG mice with aGVHD did not increase the number of detectable apoptotic cells after 12 days (Fig. 4). These data are in line with other groups reporting that MSC play no role in the induction of T cell apoptosis [17, 18, 47, 48], but are in contrast to Plumas et al., who found that human MSC induced the induction of apoptosis of activated T cells through the production of indoleamine- 2,3-dioxygenase (IDO) [46]. Despite the contradictory literature, the data herein indicated that the induction of T cell apoptosis by MSC was unlikely to be the mechanism by which MSC prolonged the survival of NSG mice with aGVHD.

243), and BPS settings were as follows: method=1.60, advanced = 10 and testing = 10. Peaks of m/z 7626, 8561 and 8608 (Fig. 2) were selected in the classified algorithm, and m/z 8608 was the root node. The intensity of m/z 8561 was down-regulated in patients with active TB compared with non-TB group, whereas m/z 7626 and 8608 were up-regulated (Table 2, Fig. 3). All the 106 samples of the training set were assigned into four terminal nodes. The samples allocated to

STI571 datasheet terminal nodes 2 and 4 were classified as active TB, but to terminal nodes 1 and 3 were classified as non-TB. For example, if an unknown sample had peaks of m/z 8608 (intensity > 14.28) and m/z 8561 (intensity < 7.00), then this sample was assigned in terminal node 2 and classified as active TB. In the training set, this model could identify 38 of 45 active TB, 60 of 61 patients with non-TB, and that is sensitivity of 98.3% STAT inhibitor and specificity of 84.4% (Table 3). The corresponding receiver operating characteristics (ROC) curve of the optimal decision

tree was supplied by the BPS. The ROC integral was 0.934 (Fig. 4). Seventy-two samples including 30 individuals of active TB group and 42 of non-TB group (Table 1) in the test set were used to validate the active TB classification tree model. And it showed that the decision tree could distinguish active TB and non-TB with the sensitivity and specificity of 85.7% and 83.3%, respectively (Table 3). The distinctive peaks among SPP-TB, SNP-TB and non-TB group also have been figured out by BMW. Surprisingly, 54 peaks were found differential expression (Table 4), and 40 of them also showed up in Table 2. In this study, we reported a classification

tree model of active TB obtained by MALDI-TOF MS analysis coupled with WCX magnetic beads pretreatment. Although only 5 μl serum of each sample was taken to perform this research, we achieved comprehensive serum proteomic fingerprint of all the individuals. Moreover, this strategy provided massive bioinformatic data that facilitate the identification of active TB biomarkers. The molecular weights of these discriminating peaks were usually under 30 kDa. And recent report Osimertinib also indicated that identifying low molecular weight proteins and peptides is valuable for developing specific assays and extending biological insight of the disease [26]. Forty-eight proteins were recognized as differential expression between active TB group and non-TB group, which suggested that a wide range of proteins might be involved in pathogenesis of active TB (Table 2). The BPS enabled us to establish an optimal classification tree model by analyzing data of the training set, and the final model contained three m/z peaks, 7626, 8561 and 8608 m/z, and can efficiently help identify patients with active TB (Fig. 1). The performance of the model achieved an accuracy of 93.4% (Fig. 4), which was better than common clinical diagnostic tests of active TB.

Perren, I.

Bravi, L. Jennen, A. Feuchtinger, J. Drouin, F. Roncaroli and N. S. Pellegata (2013) Neuropathology and Applied Neurobiology39, 256–269 Characterization of MENX-associated pituitary tumours Aims: The aim of this study is to evaluate the pathological features, serum hormone levels and ex vivo cultures of pituitary adenomas that occur in rats affected by MENX syndrome. MENX is multiple endocrine neoplasia syndrome caused by a germline MG 132 mutation in the cell cycle inhibitor p27. Characterization of MENX adenomas is a prerequisite to exploit this animal model for molecular and translational studies of pituitary adenomas. Methods: We investigated MENX pituitary adenomas with immunohistochemistry, double immunofluorescence, electron microscopy, reverse transcription

polymerase chain reaction (RT-PCR), measurement of serum hormone levels and ex vivo cultures. Results: Adenomas this website in MENX rats belong to the gonadotroph lineage. They start from 4 months of age as multiple neoplastic nodules and progress to become large lesions that efface the gland. Adenomas are composed of chromophobic cells predominantly expressing the glycoprotein alpha-subunit (αGSU). They show mitotic activity and high Ki67 labelling. A few neoplastic cells co-express gonadotropins and the transcription factor steroidogenic factor 1, together with growth hormone or prolactin and Pit-1, suggesting that they are not fully committed to one Y-27632 2HCl cell lineage. Ex vivo cultures show features similar to the primary tumour. Conclusions: Our results suggest that p27 function is critical to regulate gonadotroph cells growth. The MENX syndrome represents a unique model to elucidate the physiological and molecular mechanisms mediating the pathogenesis of gonadotroph adenomas. “
“Intracranial malignant solitary fibrous tumor (SFT) is very rare. It was identified in a 39-year-old female patient who underwent malignant transformation over 6 months. MRI revealed an 8 × 5 × 6 cm mass with heterogenous strong enhancement in the left occipital lobe. Histologic findings and immunophenotype (positive for CD34, bcl-2 and vimentin, and negative for epithelial membrane

antigen or S100 protein) of the primary tumor were typical of SFT. However, there was a focal area (<10% of tumor volume) showing hypercellularity, nuclear pleomorphism and increased Ki-67 labeling index (LI) of 10% (average, 1%). At the second operation, the recurrent tumor revealed full-blown histologic features of malignant SFT, such as infiltrative brain invasion, marked nuclear pleomorphism, frequent mitotic figures (15/10 high power fields), and high Ki-67 LI (25%). The presence of atypical histologic finding or increased Ki-67 LI in the typical SFT, although it is focal, needs to be mentioned in the diagnosis and also may require more aggressive surgical management. "
“Circumventricular organs (CVOs) are specialized ventricular structures around the third and fourth ventricles of the brain.

“
“Antibody diversity is generated by a random gene recombination process with the inherent risk of the production of autoreactive specificities. The current view suggests that B cells expressing

such specificities are negatively selected at an early developmental stage. Using the knock-in model system of the 3-83 autoreactive Proteasome inhibitor B-cell antigen receptor (BCR) in combination with precursor-BCR (pre-BCR) deficiency, we show here that the 3-83 BCR mediates efficient generation of B cells in the presence, but not the absence, of a strongly recognized auto-antigen. Experiments with mixed bone marrow chimeras showed that combining the 3-83 BCR with the corresponding auto-antigen resulted in efficient reconstitution of B-cell development in immune-deficient mice. These results suggest that B cells are positively selected by recognition of self-antigens during developmental stages that precede receptor editing. Moreover, the data indicate that the pre-BCR functions as a specialized autoreactive

BCR to initiate positive selection at a stage where the cells express immunoglobulin heavy but not light chains. Antibody diversity is achieved by random recombination of immunoglobulin (Ig) variable (V), diversity (D) and joining (J) gene segments in developing B-cell precursors 1. Antibodies are initially expressed as B-cell antigen receptors (BCRs) containing, in addition to the two identical heavy chains (HCs) and two identical light chains www.selleckchem.com/products/bmn-673.html (LCs) of the antibody, the heterodimer Ig-α/Ig-β required for signaling 2. BCR signaling is essential for the generation and selection of B cells, as the VDJ recombination process providing the basis for antibody diversity can also lead to the generation of B cells with

self-reactive receptors 3–5. Mechanisms such as receptor editing, which alters BCR specificity by secondary LC gene rearrangement, clonal deletion and anergy may operate to prevent the development of autoreactive B cells and the production of self-reactive antibodies 3, 6. We have recently shown that the effects of polyreactive BCRs recognizing multiple self-antigens are similar to those of the precursor- (pre-) BCR, suggesting such receptors to be functionally equivalent. Consequently, both polyreactive BCRs and the pre-BCR induce autonomous signaling and expansion of B cell precursors Tobramycin in vitro 7. The pre-BCR, in which the HC pairs with a surrogate LC consisting of the germ line-encoded subunits λ5 and VpreB, plays an essential role in the positive selection and expansion of precursor-B (pre-B) cells that express an HC protein 8, 9. Accordingly, a severe B-cell developmental block is observed in mice deficient for components of the surrogate LC 10, 11. Recently, we found that even a single-point mutation removing a conserved N-linked glycosylation site in the C1 domain of μHC prevented pre-BCR formation and function 12.

Furthermore, we could show that pharmacological inhibition of SphK results in reversal of CXCL4-induced monocyte survival, cytokine expression, and release of oxygen radicals, which was confirmed by the use of SphK1-specific siRNA. CXCL4-mediated rescue from apoptosis, which is accompanied by inhibition of caspases, is controlled by SphK1 and its downstream

element Erk. Taken EGFR inhibitors cancer together, these data assign SphK1 as a central regulator of acute and delayed monocyte activation and suggest SphK1 as a potential therapeutic target to suppress pro-inflammatory responses induced by CXCL4. Monocytes are members of the mononuclear phagocyte system and represent one of the most flexible cell types within the immune system. These cells are critically important in the regulation of innate and adaptive immune responses by generation of inflammatory mediators, antigen presentation, phagocytosis, and killing of microorganisms. Monocytes are highly mobile cells and can rapidly accumulate at sites of inflammation. However, a successful defense requires not only the presence of monocytes at inflammatory sites but also fast and

effective mechanisms for their activation. In previous reports we described monocyte activation by CXC chemokine ligand 4 (CXCL4; platelet factor 4) 1–3. CXCL4 belongs to the family of CXC-chemokines and is rapidly released Selumetinib in high concentrations upon platelet activation 4, 5. Although no data exist

in the literature concerning CXCL4 concentrations at a site of acute platelet activation in vivo, normal serum concentrations of CXCL4 (1–2.5 μM) 6 are sufficient to induce a full monocyte response 1. Moreover, in regions of acute platelet activation where such platelet–monocyte interaction may take place, concentrations of CXCL4 are likely to be much higher. Although CXCL4 does not induce typical chemokine responses such as chemotaxis or calcium mobilization in monocytes, CXCL4 induces ROS formation, increases phagocytosis, and protects these cells from undergoing spontaneous apoptosis Metalloexopeptidase 1, 2. Furthermore, CXCL4 treatment provokes monocytes to express and to release several pro-inflammatory cytokines and chemokines 1, 3, and stimulates the differentiation of these cells into a specific subtype of macrophages lacking HLA-DR on their surface 1. In contrast to typical CXC-chemokines, which transduces their signals via binding to a 7-transmembrane-domain G protein-coupled receptors, CXCL4-induced monocyte activation is mediated by binding to a chondroitin sulfate proteoglycan expressed on the latter cells 2, neutrophils 7, 8, T cells and mast cells (our unpublished results). It should be mentioned here that CXCR3-B, which has been described as functional CXCL4 receptor on endothelial cells 9 is not expressed on monocytes or neutrophils 2.