Other pattern-recognition receptor signaling pathways, for example RIG-I and NOD1, can also activate IRF3 and IRF5 thus ensuring robust type I IFN production in response to both viral and bacterial infections [112]. IRF7 levels are increased after type I IFN signaling, thus further amplifying type I IFN responses [113, 114]. Interestingly, IRF5 is also https://www.selleckchem.com/products/VX-770.html involved in the expression of genes important for Th17 responses, such as IL-6 and p40

(a subunit of IL-23 and IL-12), suggesting that IRF5 plays an important role both in type I IFN- and Th17-dependent diseases [111]. Notably, polymorphisms in the IRF5 gene have been repeatedly shown to associate with both SLE and SS [115-117], and an enhanced transcription of an alternatively spliced variant of IRF5 as well as increased IRF5 protein expression was demonstrated for an SLE-associated IRF5 gene haplotype [115, 116, 118, 119].

Furthermore, increased levels of IL-6, p40, and IFN-β, the genes of which are transcriptionally regulated by IRF5, are found in patients with SLE and SS (reviewed in [67, 120]), indicating that dysregulation through TLR/IRF pathways are central in systemic autoimmunity and may affect both type I interferon and Th17 responses. Additional imbalances in the TLR/IRF pathways in systemic autoimmunity arise from the circulating DNA- or RNA-containing immune complexes that activate TLR7 and TLR9 signaling after endocytosis Tipifarnib clinical trial via Fc receptors, inducing the simultaneous production of type I IFNs and cytokines important for the generation of Th17 cells (such as IL-23 and IL-6) [121]. These effects are potentially additive with those driven by the genetic polymorphisms of the factors downstream of the TLRs. Supporting evidence for a role of IRFs in systemic autoimmune disease have further been derived from mouse models; Irf5−/− mice develop less-severe disease [122] and mice lacking the IRF-specific E3 ligase TRIM21 (Trim21−/−)

develop lupus-like features such as circulating antinuclear antibodies and glomerulonephritis through an IL-23/Th17-dependent pathway [48]. Both type I IFN and IL-17 have pleiotropic effects on immune Parvulin responses, such as activation and recruitment of myeloid cells or promotion of adaptive immunity and B-cell responses, and both can prove beneficial or detrimental to the host depending on the context. Type I IFNs and IL-17 are thus crucial to the host’s innate defense mechanisms against viruses and against extracellular bacteria and fungi. However, type I IFNs and IL-17 are also implicated in the pathogenesis of several inflammatory and autoimmune diseases. Although type I IFNs have been shown to antagonize Th17 responses, it is also evident from the observations made in diseases such as psoriasis or SLE that type I IFN and Th17 responses can coexist to drive inflammation and disease [123, 124].

Ratios and fold upregulation was compared to 1 and statistical significance was calculated by a Wilcoxon-signed rank test. Cytokine data between groups were compared using a Mann–Whitney U-test. Data shown are representative of two or more independent experiments, performed in duplicate, with n = 5. Graph-Pad Prism 4.0 was used for statistics

Selleck Tanespimycin (GraphPad Software). Values of p < 0.05 were considered statistically significant. Data are given as mean ± SEM. The authors would like to thank Dr. R. de Swart for providing RSV A2, Dr. F. van Kuppeveld for providing HRV-14, Prof. R. Fouchier for providing H1N1, and Dr. J. Murk for providing Reo-3 and HAdV-3. We are also very grateful to Prof. M. Netea and Dr. J. Heldens for their critical comments on the manuscript. M. Vissers and G. Ferwerda are financially supported by the VIRGO consortium, which is approved and financially supported by the Netherlands Genomics Initiative (NGI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare no financial or commercial conflict of interest. Disclaimer: Supplementary materials have been peer-reviewed but not copyedited. "
“Acute graft-versus-host disease (GVHD) is the most important cause of mortality after allogeneic haematopoietic stem cell transplantation. Raf inhibitor Allo-reactive

T cells are the major mediators of GVHD and the process is regulated by positive and negative regulators on antigen-presenting

cells (APC). Because the significance of negative regulators in GVHD pathogenesis is not fully understood, and having discovered that syndecan-4 (SD-4) on effector T cells mediates the inhibitory function of DC-HIL on APC, we proposed that SD-4 negatively regulates the T-cell response to allo-stimulation in acute GVHD, using SD-4 knockout mice. Although not different from their wild-type counterparts ADAM7 in responsiveness to anti-CD3 stimulation, SD-4−/− T cells lost the capacity to mediate the inhibitory function of DC-HIL and were hyper-reactive to allogeneic APC. Moreover, infusion of SD-4−/− T cells into sub-lethally γ-irradiated allogeneic mice worsened mortality, with hyper-proliferation of infused T cells in recipients. Although there my be little or no involvement of regulatory T cells in this model because SD-4 deletion had no deleterious effect on T-cell-suppressive activity compared with SD-4+/+ regulatory T cells. We conclude that SD-4, as the T-cell ligand of DC-HIL, is a potent inhibitor of allo-reactive T cells responsible for GVHD and a potentially useful target for treating this disease. Allogeneic haematopoietic stem cell transplantation (HSCT) is a potentially curative option for patients with high-risk haematological malignancies, such as multiple myeloma and leukaemia.

80 Various approaches have been used to clarify the discrepancies and possible underlying mechanisms, including generation of MDDC or the analysis of peripheral blood DCs in patients with chronic HCV, by studying the effectiveness of recombinant HCV proteins or cell-culture-adapted strains of HCV on DC in vitro. Some researchers also reported that HCV-infected cells trigger a robust IFN response in PDC by a mechanism that requires active viral replication, direct cell–cell contact, and Toll-like receptor 7 (TLR7) signalling, and showed that the activated PDC supernatant inhibits HCV infection in an IFN receptor-dependent manner.81 As there is clearly controversy regarding MDC’s ability to activate

T cells, it is unclear whether on a per cell basis MDCs from HCV-infected individuals are able

to prime naive T cells. Additionally, reduced numbers of peripheral blood MDC have been observed in HCV-infected individuals and may play Vemurafenib datasheet a role in the defective response to vaccine. Canaday et al.82 specifically focused on analysis of peptide–MHC complex formation and presentation, the culmination of uptake, degradation and trafficking of antigen. They https://www.selleckchem.com/screening/tyrosine-kinase-inhibitor-library.html found that this specific antigen-presenting cell function is preserved in the setting of chronic HCV infection. As the liver is the primary site for HCV replication, DC changes in peripheral blood may or may not reflect what is happening locally at the site of infection. Several studies demonstrated enrichment Edoxaban of DC in the liver compartment compared with peripheral blood.80 Galle et al.83 employed electron microscopy, immunohistochemistry and immunofluorescence to show that DC are indeed enriched in the livers of HCV-infected individuals. Wertheimer et al.84 also showed a clear enrichment of DC in the intrahepatic compartment

compared with the peripheral circulation. To investigate the contribution of intrahepatic PDC and MDC to local immune responses during HCV infection, Lai et al.85,86 developed methods to isolate and characterize MDC and PDC from human liver. The MDC from HCV-infected liver demonstrated greater expression of MHC class II, CD86 and CD123, that were more efficient stimulators of allogeneic T cells and secreted less IL-10. In contrast, PDC were present at lower frequencies in HCV-infected liver and expressed higher levels of the regulatory receptor BDCA-2. In HCV-infected liver, the combination of enhanced MDC function and a reduced number of PDC might contribute to viral persistence in the face of persistent inflammation. Nattermann et al.87 demonstrated that chronic HCV infection, associated with intrahepatic DC enrichment, migration of DC is markedly affected by interaction of HCV E2 with CD81. A two-photon confocal microscopic analysis revealed that DC and T lymphocytes were rapidly recruited within human liver slices undergoing an ex vivo HCV infection.

The heavy burden of cardiovascular disease and diabetes was assessed by Snyder et al.25 who compared awareness, treatment and control of hypertension, elevated low-density lipoprotein (LDL) cholesterol and diabetes in non-CKD and CKD populations. Dividing the CKD population by cardiovascular disease status and CKD stage, they showed that likelihood of hypertension was 5 times higher for stage 1–2 CKD patients than for non-CKD counterparts, and 1.4–2.5 times higher for stages 3–4. Among people with hypertension, awareness of the condition was 40% lower for those with stage 1–2 CKD compared with the non-CKD population, and treatment of defined hypertension was also 40% lower. For stage 1–2 CKD patients, hypertension

was controlled (defined as blood pressure <140/90 mmHg) for only one in five, and control was 50% lower for stage 3–4 CKD patients compared with the non-CKD population. Use of kidney-protective CHIR-99021 medications (angiotensin-converting enzyme inhibitors and angiotensin receptor blocking agents) was half as likely among stage 1–2 CKD patients and 20% less likely among stage 3–4 CKD see more patients than in the non-CKD population. These observations from the US National Health and Nutrition Examination Survey (NHANES) random population sample suggest that CKD patients receive inadequate hypertension care, and are thus at risk for the observed high cardiovascular event rates.14,15 Awareness,

treatment and control of hypercholesterolaemia is also poor in the CKD population.

Rates of LDL cholesterol above 100 mg/dL are highest for stage 3–4 CKD patients, who also have the lowest awareness and lowest odds of treatment, and only 14% achieve control (LDL cholesterol less than 100 mg/dL). These patients are thus predisposed to higher risk of cardiovascular events, which increase exactly when hypercholesterolaemia treatment and control are lowest. These observations support consideration of early and comprehensive identification and intervention strategies, with else treatment guidelines comparable to the general population,26 until such time as clinical trial results exist to guide therapy. Further, glycaemic control in the CKD population with diabetes was lowest in stage 1–2 CKD compared with non-CKD counterparts. Additional surveillance data show that only 60% of the Medicare population with diagnosed diabetes receives two annual HbA1c tests to monitor glycaemic control. This percentage is even lower in Taiwan, a population with the highest ESRD incidence in the world.27 Only one in five diabetic patients in the USA receives screening for kidney disease with at least one microalbuminuria test per year, as do only 40% of diabetic patients in Taiwan. These numbers provide further evidence of less-than-needed care for this high-risk population. Several investigators report on CKD risk factors from the NHANES random population sample and other community databases.

In addition, we investigated whether the effect exerted by these antigens in the modulation of the angiogenesis factors was direct or through other inflammatory mediators, such as nitric oxide. iNOS is known to regulate VEGF expression, and thereby angiogenesis (33–35). As alveolar macrophages release nitric oxide in response to helminthic antigens (21), may be inhibition of iNOS

could be decreased VEGF production. We confirmed the Autophagy Compound Library concentration relationship between the production of nitric oxide and the angiogenesis factors by using inhibitors of the ONSi (l-NAME and l-canavanine), which inhibited the expression of angiogenesis factors. In summary, this study demonstrated that angiogenesis factors mTOR inhibitor play a role in the primary infection by S. venezuelensis as the inhibition by endostatin produced a decrease in the number of larvae and females. Direct mechanisms with diminution of angiogenesis factors and indirect mechanisms with decrease of the number of eosinophils could be related to the protection from the parasitic infection. Angiogenic factors are induced by somatic antigens of third stage larvae of S. venezuelensis. A positive relationship between angiogenesis factors

and nitric oxide has been observed using nitric oxide synthase inhibitors. This work was supported by the projects of Junta Castilla y León SA116A08. Shariati F fellowship, acknowledges financial support from Ministry of science of IR Iran. “
“Bacterial biofilms are imaged by various kinds of microscopy including confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). One HSP90 limitation of CLSM is its restricted magnification, which is resolved by the use of SEM that provides high-magnification spatial images of how the single bacteria are located and interact within the biofilm. However, conventional SEM is limited by the requirement of dehydration of the samples during preparation.

As biofilms consist mainly of water, the specimen dehydration might alter its morphology. High magnification yet authentic images are important to understand the physiology of biofilms. We compared conventional SEM, Focused Ion Beam (FIB)-SEM and CLSM with SEM techniques [cryo-SEM and environmental-SEM (ESEM)] that do not require dehydration. In the case of cryo-SEM, the biofilm is not dehydrated but kept frozen to obtain high-magnification images closer to the native state of the sample. Using the ESEM technique, no preparation is needed. Applying these methods to biofilms of Pseudomonas aeruginosa showed us that the dehydration of biofilms substantially influences its appearance and that a more authentic biofilm image emerges when combining all methods. Bacteria are found in at least two distinct states – either as planktonic or sessile cells.

Our results demonstrate that different MC types, such

as BMMCs, mature PMCs and human MCs, can directly communicate with CD4+CD25+ Tregs and can be subject to Treg-mediated suppression. These findings warrant our deeper investigation of how the MC–Treg functional interplay takes place on a single-cell level. We found substantial differences between WT Tregs and OX40-deficient Tregs in forming see more conjugates with both BMMCs and PMCs that reflect differences in the MC response to IgE/Ag activation. While MCs made sporadic contacts in the presence of OX40-deficient Tregs, accompanied by Ag-induced degranulation, MCs incubated with WT Tregs showed an increase in numbers of contacts and displayed a lack of evident, classical signs of exocytosis. Thus, the OX40–OX40L Selumetinib concentration axis increases the ability of cells to interact each other and contributes to support a long lasting interaction. Nevertheless, the reduced but still evident ability of MCs to make long-lasting contacts with Tregs lacking OX40 molecules suggests that other receptor–ligand counterparts could be involved in the initial formation of this synaptic contact, likely through PD1-PDL1 18, 28, 29 and Notch ligands-Notch1 30, 31 expressed on Tregs and MCs respectively. We have previously demonstrated

that FcεRI-dependent Ca2+ mobilization in MCs is impaired in the presence of WT but not OX40-deficient Tregs 4. The Treg-mediated effect affects neither PLC-γ2 activation nor the emptying of intracellular Ca2+ stores but prevents the uptake of extracellular Ca2+. Thus, this inhibition is likely to result from the absolute requirement of the MC secretory granule fusion machinery for Ca2+ influx, as the release of Ca2+ from intracellular stores alone is not sufficient to properly activate secretory fusion proteins 32. Here,

we demonstrate that the physical interaction with a single Treg leads to the inhibition of Ca2+ signaling in MCs. In the presence of WT but not OX40−/− Tregs, the reduced Ca2+ uptake was accompanied by the inhibition of early preformed mediator-release from IgE/Ag-activated MCs while later events of MC activation are not affected. Moreover, a more detailed analysis obtained with electron microscopy confirmed that ‘classical’ degranulation Metalloexopeptidase was inhibited when MCs were in close contact with Tregs, but it also indicated that MCs probably underwent selective mediator secretion throughout PMD, rather than classical exocytosis. PMD refers to a particulate pattern of cell degranulation, which was formerly described in basophils, MCs and eosinophils 33, 34. This ultrastructurally defined secretory model implies a discrete release of granule particles from storage granules without granule fusion with the plasma membrane. Secretion occurs by translocation of loaded vesicles or by means of vesiculotubular structures.

STATISTICA® StatSoft, Inc. (StatSoft Scandinavia AB, Uppsala, Sweden) 9.0 software package was used selleck for all statistical analyses. Positively skewed variables were logarithmically transformed prior to analysis. Values are presented as mean ± SD. The

study was approved by the Ethics Committee at Huddinge University Hospital, Stockholm, Sweden. The research was performed in accordance with institutional guidelines of the Karolinska Institute and in accordance with the Declaration of Helsinki. All subjects gave their informed consent. As shown in Table 1, the level of ascorbate in plasma increased significantly after treatment with ascorbate. Likewise, the level of α-tocopherol in plasma increased after treatment with vitamin E, whereas measured levels of retinol remained unchanged. As shown in Table 2, inhalation of cigarette smoke induced a significant reduction in capillary blood flow velocity. This effect of smoking was very prompt both before (p < 0.0007) and after treatment with ascorbate (p < 0.0004). However, there was no significant difference in terms of relative reduction in CBV before or after intervention by either of the antioxidants. The reduction was 65% before ascorbate and 60% after ascorbate (ns). At baseline, TtP was significantly prolonged after inhalation of cigarette smoke, an increase in TtP from 7.3 to 10.6 seconds (p < 0.05). When comparing

the response to provocation by PRH before and after two weeks of treatment with ascorbate, there was a highly significant shortening of TtP Selleck NU7441 as compared with baseline: 7.3 seconds vs 5.2 seconds (p < 0.002). Furthermore, the TtP in response to smoking after treatment with ascorbate was prolonged from 5.2 to 7.4 seconds (p < 0.002). The relative change in response to smoking did not differ between subjects treated or not treated with ascorbate (ns). The same experimental protocol was repeated in volunteers using vitamin E. Again, there was an effect on resting CBV with a similar effect of acute smoke inhalation on CBV as for ascorbate. The reduction in CBV after smoking was highly significant: from 0.72 ± 0.24 to 0.40 ± 0.22 mm/sec (p < 0.000008). Concordant with the results of treatment

with ascorbate, there was no difference L-gulonolactone oxidase in the response of CBV to the effects of smoke inhalation before and after treatment with vitamin E, i.e., it was not possible to demonstrate any significant effect on the reduction in CBV in response to smoking before or after the two-week treatment with vitamin E. The baseline TtP before treatment with vitamin E was similar to before ascorbate, 7.0 ± 3.0 seconds compared to 7.3 seconds (ns). However, there was no difference in TtP before or after the two-week treatment with vitamin E, 7.0 ± 3.0 seconds vs 6.8 ± 2.6 seconds (ns). Baseline CBV before either treatment did not differ (ns). In contrast to baseline measurements, the CBV increased significantly after treatment with ascorbate, from 0.64 ± 0.33 to 1.00 ± 0.53 mm/sec (p < 0.

We performed Ab staining and flow cytometric analysis of freshly isolated cells from spleen, LNs, and BM of B6 mice, as shown in Figure 1. We gated on CD44high CD8+ T cells (Fig. 1A), and examined CD127, CD132, and TSLP-R median fluorescence intensity (MFI) of cells from spleen, LNs, and BM (Fig. 1B and C). In line with

our previous findings [[10, 11]], we found that CD127 MFI was significantly lower in BM than in either spleen www.selleckchem.com/products/Romidepsin-FK228.html or LNs CD44high CD8+ T cells. In contrast to CD127, CD132 was only slightly higher in LNs than in spleen and BM, whereas TSLP-R levels were always low (Fig. 1C). As a positive control for TSLP-R, we stained in parallel CD19+CD25+ cells from BM samples [[25]] and found that their average MFI values were 182 for TSLP-R and 32 for isotype control (data not shown). To better understand the difference between BM and the other two organs, we separately analyzed the CD122int/low and CD122high subset. In agreement with our previous findings on CD8+ T cells [[11]], the percentage of CD122high cells within CD44high CD8+ T

cells was higher in the BM than in either spleen or LNs (Supporting Information Selleck BTK inhibitor Fig. 1A and B). In the BM, both CD122int/low and CD122high subset had a decreased CD127 membrane expression (Supporting Information Fig. 1C). Our findings suggest that CD127 is specifically downmodulated by CD44high CD8+ T cells in the BM.

Considering that the lower membrane CD127 expression in the BM likely reflects CD44high CD8+ T-cell activation in this organ, we investigated whether IL-7 and IL-15 were required for such phenomenon by studying genetically modified mice. We observed that in IL-7 KO mice the CD127 MFI difference between spleen and BM was even higher than in wild-type (WT) mice, showing that CD127 downmodulation in the BM did not require IL-7; LNs were not examined because they are absent in IL-7 KO mice (Fig. 2B). In IL-15 KO mice, the highest level of CD127 membrane expression by CD44high CD8+ T cells was found in the BM (Fig. 2C). In IL-15Rα KO, CD127 membrane expression was similar in the three organs ifenprodil examined (Fig. 2D). Since the genetic deficiency in IL-15/IL-15Rα predominantly affects the CD122high cells [[26-28]], we separately examined the CD122int/low and CD122high cells and found that both subsets did not display the normal CD127 downmodulation in the BM (Fig. 3). In IL-15 KO mice, CD122int/low cells expressed higher membrane CD127 in the BM than in spleen and LNs (Fig. 3) Our results show that IL-15 but not IL-7 is a regulator of CD127 membrane expression by BM CD44high CD8+ T cells. Since endogenous memory CD8+ T cells do not develop normally in IL-15- and IL-15Rα-KO mice [[26, 29]], we performed adoptive transfer experiments. We injected intravenously (i.v.

The induction of the unfolded protein response (UPR) in C. difficile infection has not been investigated; nor has pro-survival signalling been a major focus of studies on this infection. A number of reports have implicated the UPR in pro-inflammatory responses in general,[15, 16] and in intestinal inflammation CHIR99021 in particular.[17-19]

More specifically, X-box-binding protein 1 (XBP1),[17] activating transcription factor 6 (ATF6)[18] and eukaryotic initiation factor 2α (eIF2α) phosphorylation[19] each play a protective role against dextran sodium sulphate-induced colitis. The UPR is a concerted adaptive programme that counters endoplasmic reticulum (ER) stress by down-regulating the synthesis of secreted proteins, up-regulating ER chaperone and

foldase levels, and activating ER-associated degradation, hence easing the burden on the stressed ER by decreasing its protein load, increasing its folding capacity and eliminating irreparably misfolded proteins.[20, 21] In higher eukaryotes, PRKR-Like Endoplasmic Reticulum Kinase (PERK), Inositol-Requiring Enzyme 1 (IRE1) and ATF6 act as the proximal transducers of ER stress. Each of these serves a distinct role in the UPR. The most rapid outcome is translational attenuation. It is mediated by activated PERK through the phosphorylation of eIF2α and takes effect as early as 30 min after exposure to ER stress.[22, 23] The GADD34/PP1 complex provides feedback inhibition of this process Mitomycin C ic50 by specifically promoting eIF2α dephosphorylation.[24, 25] IRE1 exerts its cytoprotective effect mainly by removing a 26-base intron from the mRNA encoding XBP1.[26, 27] The spliced Xbp1 encodes a potent transcription factor whose targets encode several proteins involved in ER protein folding 5-Fluoracil cell line and the degradation of

misfolded ER proteins.[28, 29]In response to ER stress, the transmembrane portion of ATF6 is cleaved by S1P and S2P proteases that reside in the Golgi apparatus.[30] The cleaved fragment moves to the nucleus and, mainly in parallel with XBP1, up-regulates genes that increase ER chaperone activity and the degradation of misfolded proteins.[31, 32] The protective roles of eIF2α phosphorylation, XBP1 and ATF-6 in mouse models of chemically induced colitis,[17-19] serve as our rationale for investigating the potential effect of C. difficile infection on different elements of the UPR. Here we have used the mouse model of C. difficile infection originally reported by Chen et al.,[33] and previously studied in our group,[34-36] to address the following unanswered questions. First, how does the host expression of chemokines, cytokines, anti-microbial peptides and other epithelial-associated genes change during acute C.

However, LY2109761 all the other clinical features presented in Table 1 differed significantly among our study groups. Fetal growth restriction was absent in healthy pregnant women, whereas the frequency of this condition was 18·3% in the pre-eclamptic group. Twenty-one women had severe pre-eclampsia and five patients experienced early onset of the disease.

In our pre-eclamptic group, multiparous women had significantly higher age [32 (29–35) versus 28 (25–31) years, P < 0·001] and pre-pregnancy body mass index (BMI) [27·2 (25·5–29·0) versus 23·1 (19·8–26·1) kg/m2, P < 0·05] than primiparous women. The laboratory parameters of the study subjects are displayed in Table 2. As can be seen in the table, there were significant differences in most of the measured laboratory parameters among the three study groups except for serum aspartate aminotransferase (AST) activity. As shown in Fig. 1a,b, plasma levels of ficolin-2 were significantly lower in healthy pregnant

than in healthy non-pregnant women, while ficolin-3 levels did not differ significantly between the two groups. Furthermore, pre-eclamptic patients had significantly FDA approved Drug Library lower ficolin-2 and ficolin-3 concentrations than healthy non-pregnant and pregnant women. Using the receiver operating characteristic (ROC) curve analysis, we determined cut-off values for plasma levels of ficolin-2 (<2·84 µg/ml; sensitivity: 70·2%, specificity: 66·1%) and ficolin-3 (<24·0 µg/ml; sensitivity: 68·3%, specificity: 54·2%) to discriminate pre-eclamptic patients from healthy pregnant women. Both low ficolin-2 and ficolin-3 levels were associated significantly with pre-eclampsia [OR (95% CI) for ficolin-2: 4·58 (2·07–10·1), P < 0·001; for ficolin-3: 2·56 (1·21–5·40), P < 0·05], even after adjustment for maternal age, BMI and gestational

age at blood draw in multiple logistic regression analysis [adjusted OR with 95% CI for ficolin-2: 8·74 (2·90–26·4), P < 0·001; for ficolin-3: 3·30 (1·24–8·77), P < 0·05]. In the group of pre-eclamptic patients, no statistically significant differences were found in plasma levels of ficolin-2 and ficolin-3 between patients with mild and severe pre-eclampsia, selleck between patients with late and early onset of the disease or between pre-eclamptic patients with and without fetal growth restriction (data not shown). We also investigated whether plasma ficolin-2 and ficolin-3 concentrations of the study participants were related to their clinical features and laboratory parameters by calculating the Spearman’s rank order correlation coefficients (continuous variables) or by Mann–Whitney U-test (categorical variables). In healthy pregnant women, there was a statistically significant positive correlation between plasma ficolin-2 and serum PlGF concentrations (Spearman’s R = 0·33, P < 0·05), while a significant inverse correlation was observed between their ficolin-2 and sFlt-1 levels (R = −0·59, P < 0·001; Fig. 2a).