Soluble Form Of CD14 Research Articles

New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy.

Central Illustration : New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy. Cardiovascular diseases (CVDs) are relevant to the management of breast cancer treatment since a substantial number of patients develop these complications after chemotherapy. This study aims to evaluate new cardiovascular biomarkers, namely CXCL-16 (C-X-C motif ligand 16), FABP3 (fatty acid binding protein 3), FABP4 (fatty acid binding protein 4), LIGHT (tumor necrosis factor superfamily member 14/TNFS14), GDF-15 (Growth/differentiation factor 15), sCD4 (soluble form of CD14), and ucMGP (uncarboxylated Matrix Gla-Protein) in breast cancer patients treated with doxorubicin (DOXO). This case-control study was conducted in an oncology clinic that included 34 women diagnosed with breast cancer and chemotherapy with DOXO and 34 control women without cancer and CVD. The markers were determined immediately after the last cycle of chemotherapy. The statistical significance level adopted was 5%. The breast cancer group presented higher levels of GDF-15 (p<0.001), while control subjects had higher levels of FABP3 (p=0.038), FABP4 (p=0003), sCD14, and ucMGP (p<0.001 for both). Positive correlations were observed between FABPs and BMI in the cancer group. GDF15 is an emerging biomarker with potential clinical applicability in this scenario. FABPs are proteins related to adiposity, which are potentially involved in breast cancer biology. sCD14 and ucMGP engage in inflammatory and vascular calcification. The evaluation of these novel cardiovascular biomarkers could be useful in the management of breast cancer chemotherapy with DOXO.

Soluble CD14 is subtype-dependent in serum but not in cerebrospinal fluid in people with HIV

Monocytes and macrophages activation are crucial in human immunodeficiency virus (HIV) central nervous system (CNS) infection and HIV associated neurocognitive disorders (HAND) pathogenesis. The soluble form of CD14 (sCD14) is a marker of monocyte activation. We hypothesized that sCD14 levels would be lower in people with HIV-1 subtype C (HIV-1C) than in HIV-1B owing to a variant Tat cysteine dimotif (C30S31) with reduced chemotactic activity. A total of 68 paired cerebrospinal fluid (CSF) and blood samples from people with HIV (PWH); 27 samples of the HIV-1B subtype and 40 of the non-B HIV-1 subtypes (including 26,HIV-1C), and 18 HIV-negative controls were included. sCD14 levels were quantified using a high-sensitivity enzyme-linked immunosorbent assay. sCD14 increase in serum, but not in CSF, was higher in samples from HIV-1B than HIV-1C (p = 0.002; Cohen's d, 0.7). CSF or serum sCD14 values were not correlated with global deficit score or specific cognitive domains. The impact of HIV-1 on monocyte stimulation biomarkers evaluated by sCD14 in serum was subtype-dependent, higher in HIV-1B than HIV-1C, consistent with reduced chemotactic activity as hypothesized.

Plasma Soluble CD14 Subtype Levels Are Associated With Clinical Outcomes in Critically Ill Subjects With Coronavirus Disease 2019.

In bacterial sepsis, CD14 and its N-terminal fragment (soluble CD14 subtype, "Presepsin") have been characterized as markers of innate immune responses and emerging evidence has linked both to coronavirus disease 2019 pathophysiology. Our aim was to determine the relationship between the soluble form of CD14 and soluble CD14 subtype plasma levels, coronavirus disease 2019 status, and coronavirus disease 2019-related outcomes. A prospective cohort study. ICUs in three tertiary hospitals in Seattle, WA. Two-hundred four critically ill patients under investigation for coronavirus disease 2019. We measured plasma soluble CD14 and soluble CD14 subtype levels in samples collected upon admission. We tested for associations between biomarker levels and coronavirus disease 2019 status. We stratified by coronavirus disease 2019 status and tested for associations between biomarker levels and outcomes. Among 204 patients, 102 patients had coronavirus disease 2019 and 102 patients did not. In both groups, the most common ICU admission diagnosis was respiratory failure or pneumonia and proportions receiving respiratory support at admission were similar. In regression analyses adjusting for age, sex, race/ethnicity, steroid therapy, comorbidities, and severity of illness, soluble CD14 subtype was 54% lower in coronavirus disease 2019 than noncoronavirus disease 2019 patients (fold difference, 0.46; 95% CI, 0.28-0.77; p = 0.003). In contrast to soluble CD14 subtype, soluble CD14 levels did not differ between coronavirus disease 2019 and noncoronavirus disease 2019 patients. In both coronavirus disease 2019 and noncoronavirus disease 2019, in analyses adjusting for age, sex, race/ethnicity, steroid therapy, and comorbidities, higher soluble CD14 subtype levels were associated with death (coronavirus disease 2019: adjusted relative risk, 1.21; 95% CI, 1.06-1.39; p = 0.006 and noncoronavirus disease 2019: adjusted relative risk, 1.19; 95% CI, 1.03-1.38; p = 0.017), shock, and fewer ventilator-free days. In coronavirus disease 2019 only, an increase in soluble CD14 subtype was associated with severe acute kidney injury (adjusted relative risk, 1.23; 95% CI, 1.05-1.44; p = 0.013). Higher plasma soluble CD14 subtype is associated with worse clinical outcomes in critically ill patients irrespective of coronavirus disease 2019 status though soluble CD14 subtype levels were lower in coronavirus disease 2019 patients than noncoronavirus disease 2019 patients. Soluble CD14 subtype levels may have prognostic utility in coronavirus disease 2019.

Soluble CD83 Regulates Dendritic Cell-T Cell Immunological Synapse Formation by Disrupting Rab1a-Mediated F-Actin Rearrangement.

Dendritic cell–T cell (DC-T) contacts play an important role in T cell activation, clone generation, and development. Regulating the cytoskeletal protein rearrangement of DCs can modulate DC-T contact and affect T cell activation. However, inhibitory factors on cytoskeletal regulation in DCs remain poorly known. We showed that a soluble form of CD83 (sCD83) inhibited T cell activation by decreasing DC-T contact and synapse formation between DC and T cells. This negative effect of sCD83 on DCs was mediated by disruption of F-actin rearrangements, leading to alter expression and localization of major histocompatibility complex class II (MHC-II) and immunological synapse formation between DC and T cells. Furthermore, sCD83 was found to decrease GTP-binding activity of Rab1a, which further decreased colocalization and expression of LRRK2 and F-actin rearrangements in DCs, leading to the loss of MHC-II at DC-T synapses and reduced DC-T synapse formation. Further, sCD83-treated DCs alleviated symptoms of experimental autoimmune uveitis in mice and decreased the number of T cells in the eyes and lymph nodes of these animals. Our findings demonstrate a novel signaling pathway of sCD83 on regulating DC-T contact, which may be harnessed to develop new immunosuppressive therapeutics for autoimmune disease.

Mononuclear Phagocyte Activation Is Associated With the Immunopathology of Psoriasis.

Psoriasis is a chronic, inflammatory disease affecting the skin and joints. The pathogenesis of this disease is associated with genetic, environmental and immunological factors, especially unbalanced T cell activation and improper keratinocyte differentiation. Psoriatic lesion infiltrate is composed of monocytes and T cells, and most studies have focused on the participation of T cells in the pathogenesis of this disease. Here we investigated the contribution of mononuclear phagocytes in the immunopathology observed in psoriatic patients. Significant increases in the levels of TNF, IL-1β, CXCL9, as well as the soluble forms of CD14 and CD163, were observed within the lesions of psoriatic patients compared to skin biopsies obtained from healthy individuals. Moreover, we found an association between the levels of CCL2, a monocyte attractant chemokine, and disease severity. In conclusion, our findings suggest a potential role for mononuclear phagocytes in the pathogenesis of psoriasis.

Evaluation of four clinical laboratory parameters for the diagnosis of myalgic encephalomyelitis

BackgroundMyalgic encephalomyelitis (ME) is a complex and debilitating disease that often initially presents with flu-like symptoms, accompanied by incapacitating fatigue. Currently, there are no objective biomarkers or laboratory tests that can be used to unequivocally diagnosis ME; therefore, a diagnosis is made when a patient meets series of a costly and subjective inclusion and exclusion criteria. The purpose of the present study was to evaluate the utility of four clinical parameters in diagnosing ME.MethodsIn the present study, we utilized logistic regression and classification and regression tree analysis to conduct a retrospective investigation of four clinical laboratory in 140 ME cases and 140 healthy controls.ResultsCorrelations between the covariates ranged between [− 0.26, 0.61]. The best model included the serum levels of the soluble form of CD14 (sCD14), serum levels of prostaglandin E2 (PGE2), and serum levels of interleukin 8, with coefficients 0.002, 0.249, and 0.005, respectively, and p-values of 3 × 10−7, 1 × 10−5, and 3 × 10−3, respectively.ConclusionsOur findings show that these parameters may help physicians in their diagnosis of ME and may additionally shed light on the pathophysiology of this disease.

An Expanded Neuroimmunomodulation Axis: sCD83-Indoleamine 2,3-Dioxygenase—Kynurenine Pathway and Updates of Kynurenine Pathway in Neurologic Diseases

Many neurologic diseases are related to autoimmune dysfunction and a variety of molecules or reaction pathways are involved in the regulation of immune function of the nervous system. Soluble CD83 (sCD83) is the soluble form of CD83, a specific marker of mature dendritic cell, which has recently been shown to have an immunomodulatory effect. Indoleamine 2,3-dioxygenase (IDO; corresponding enzyme intrahepatic, tryptophan 2,3-dioxygenase, TDO), a rate-limiting enzyme of extrahepatic tryptophan kynurenine pathway (KP) participates in the immunoregulation through a variety of mechanisms solely or with the synergy of sCD83, and the imbalances of metabolites of KP were associated with immune dysfunction. With the complement of sCD83 to IDO-KP, a previously known immunomodulatory axis, this review focused on an expanded neuroimmunomodulation axis: sCD83-IDO-KP and its involvement in nervous system diseases.

Soluble CD163 in intracerebral hemorrhage: biomarker for perihematomal edema.

ObjectivePatients with intracerebral hemorrhage (ICH) may elaborate varying degrees of perihematomal edema (PHE), requiring closer monitoring and a higher intensity of treatment. Here, we explore whether the soluble form of CD163, a scavenger receptor responsible for hemoglobin sequestration, can serve as a prognostic biomarker of PHE development and poor outcome after ICH.MethodsOur study cohort was comprised of 51 primary age‐ and sex‐matched ICH patients with moderate‐sized, hypertensive deep hemorrhages. Patients were part of a prospective ICH registry cataloguing admission data along with functional outcomes. We measured sCD163 levels in serial serum and cerebrospinal fluid (CSF) samples obtained at prespecified timepoints. Descriptive statistics, including a generalized estimating equation for longitudinal data, were used to analyze sCD163 in relation to ICH outcomes.ResultsAcute serum sCD163 (<48 h postictus) was significantly elevated in ICH patients compared to both acute neurological event controls (P = <0.001) and healthy controls (P = 0.003). As predicted, acute serum sCD163 levels were significantly associated with both hematoma volume expansion (P = 0.009) and PHE expansion (P = 0.002). Further examination determined that patients with high PHE expansion had poorer modified Rankin Scale scores at discharge (P = 0.024), and circulating sCD163 levels were found to be significantly lower in patients with high‐level PHE expansion.InterpretationAcute sCD163 levels may be a useful biomarker for the acute identification of patients at risk for hematoma expansion, perihematomal edema expansion and poorer short‐term outcomes.

A Kinetic Study of CD83 Reveals an Upregulation and Higher Production of sCD83 in Lymphocytes from Pregnant Mice.

For the normal development of pregnancy, a balance between immune tolerance and defense is crucial. However, the mechanisms mediating such a balance are not fully understood. CD83 is a transmembrane protein whose expression has been linked to anti-inflammatory functions of T and B cells. The soluble form of CD83, released by cleavage of the membrane-bound protein, has strong anti-inflammatory properties and was successfully tested in different mouse models. It is assumed that this molecule contributes to the establishment of immune tolerance. Therefore, we postulated that the expression of CD83 is crucial for immune tolerance during pregnancy in mice. Here, we demonstrated that the membrane-bound form of CD83 was upregulated in T and B cells during allogeneic murine pregnancies. An upregulation was also evident in the main splenic B cell subtypes: marginal zone, follicular zone, and transitional B cells. We also showed that there was an augmentation in the number of CD83+ cells toward the end of pregnancy within splenic B and CD4+ T cells, while CD83+ dendritic cells were reduced in spleen and inguinal lymph nodes of pregnant mice. Additionally, B lymphocytes in late-pregnancy presented a markedly higher sensitivity to LPS in terms of CD83 expression and sCD83 release. Progesterone induced a dosis-dependent upregulation of CD83 on T cells. Our data suggest that the regulation of CD83 expression represents a novel pathway of fetal tolerance and protection against inflammatory threats during pregnancy.

SCD163 levels as a biomarker of disease severity in leprosy and visceral leishmaniasis.

BackgroundCD163, receptor for the haptoglobin–hemoglobin complex, is expressed on monocytes/macrophages and neutrophils. A soluble form of CD163 (sCD163) has been associated with the M2 macrophage phenotype, and M2 macrophages have been shown to down-modulate inflammatory responses. In particular, previous studies have shown that M2 is closely associated with the most severe clinical presentation of leprosy (i.e. lepromatous leprosy (LL)), as well as tuberculosis. We hypothesized that sCD163 correlates with severity of diseases caused by intracellular pathogens.Methodology/Principal findingsTo assess this hypothesis, sCD163 levels were measured in the serum of leprosy and visceral leishmaniasis (VL) patients stratified by severity of the clinical presentation. sCD163 levels were significantly higher in patients with these diseases than those observed in healthy control individuals. Further analyses on infection and disease status of leprosy and VL patients revealed a clear association of sCD163 levels with clinical parameters of disease severity. In vitro culture assays revealed that Leishmania infection induced CD163 expression on the surface of both monocyte/macrophages and neutrophils, suggesting these cells as possible sources of sCD163. FACS analyses shows that the cells expressing CD163 produces both TNF-α and IL-4.Conclusions/SignificanceTaken together, our results reveal sCD163 as a potential biomarker of severity of diseases caused by intracellular pathogens M. leprae and Leishmania spp. and have a modulatory role, with a mix of an inflammatory property induced by TNF-α release, but that potentially induces an anti-inflammatory T cell response, related to IL-4 release.

CD163 levels, pro- and anti-inflammatory cytokine secretion of monocytes in children with pulmonary tuberculosis.

Childhood tuberculosis (TB) comprises an important part of the world's TB burden. Monocytes set up the early phase of infection because of innate immune responses. Understanding the changes in monocyte subsets during multisystem infectious diseases may be important for the development of novel diagnostic and therapeutic strategies. The aim of this study was to evaluate the monocyte phenotype together with the cytokine secretion profiles of children with pulmonary tuberculosis. Thirteen patients with pulmonary TB were enrolled as study group, and 14 healthy subjects as control group. Surface expressions of CD16, CD14, CD62L, CD163, CCR2, and HLA-DR of monocytes were analyzed by flow cytometry. The presence of IFN-γ, TNF-α, IL-10, IL-12, IL-23, and soluble form of CD163 (sCD163) in the antigen- and LPS-stimulated whole blood culture supernatants were detected using ELISA and Luminex. Higher percentages of CD14++ CD16+ and CD14+ CD16++ monocyte subsets, and CCR2, CD62L and CD163 expression on circulating monocytes in children with pulmonary tuberculosis were obtained. Diminished levels of ESAT-6/CFP-10-induced IL-10 and increased levels of TB-antigen and LPS-stimulated sCD163 were found in childhood with pulmonary TB. High expression of CD14++ CD16+ , CD14+ CD16++ , CD14+ CCR2+ , and CD14+ CD62L+ cells in childhood TB, and monocyte-derived cytokines reflected both pro- and anti-inflammatory profiles. Higher sCD163 and CD14+ CD163+ monocytes might help physicians in the differential diagnosis of pulmonary TB in children. Pediatr Pulmonol. 2017;52:675-683. © 2016 Wiley Periodicals, Inc.

CD163 promotes hematoma absorption and improves neurological functions in patients with intracerebral hemorrhage.

Clinical outcomes are positively associated with hematoma absorption. The monocyte-macrophage scavenger receptor, CD163, plays an important role in the metabolism of hemoglobin, and a soluble form of CD163 is present in plasma and other tissue fluids; therefore, we speculated that serum CD163 affects hematoma absorption after intracerebral hemorrhage. Patients with intracerebral hemorrhage were divided into high- and low-level groups according to the average CD163 level (1,977.79 ± 832.91 ng/mL). Compared with the high-level group, the low-level group had a significantly slower hematoma absorption rate, and significantly increased National Institutes of Health Stroke Scale scores and modified Rankin Scale scores. These results suggest that CD163 promotes hematoma absorption and the recovery of neurological function in patients with intracerebral hemorrhage.

Circulating classical CD14++CD16- monocytes predict shorter time to initial treatment in chronic lymphocytic leukemiapatients: Differential effects of immune chemotherapy on monocyte-related membrane and soluble forms of CD163.

Three main monocyte subsets: classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++, differentially regulate tumor growth and survival. Thereby, in the present study we aimed to determine the role of distinct monocyte subsets in the prognostication of chronic lymphocytic leukemia (CLL). Moreover, we set out to analyze the effects of standard immune chemotherapy on different monocyte subsets and levels of membrane-associated and soluble forms of CD163, a monocyte/macrophage-related immunomodulatory protein. We demonstrated that the number of peripheral blood classical CD14++CD16- monocytes assessed at the time of diagnosis was negatively correlated with lymphocytosis and was decreased in the CLLpatients who required immediate treatment as opposed to patients who qualified to 'watch and wait' strategy. Notably, lower baseline levels of classical CD14++CD16- monocytes in CLL patients who were qualified for 'watch and wait' therapy were associated with shorter time to initial treatment. Notably, therapy with rituximab, cyclophosphamide and fludarabine resulted in a significant reduction in the number of non-classical CD14+CD16++ monocytes and soluble form of CD163 but upregulation of membrane-associated monocyte CD163. Our data indicate that distinct monocyte subsets and two forms of CD163 are differentially modulated by both CLL and immune chemotherapy. Moreover, we proposed that quantification of classical monocytes at the time of diagnosis contributes to better prognostication of CLLpatients.

Macrophage-derived soluble CD163 level in young patients with Gaucher disease: relation to phenotypes, disease severity and complications.

Bone and lung involvement are two major causes of morbidity in Gaucher disease (GD). The soluble form of CD163 (sCD163) is a valuable diagnostic biomarker for monitoring diseases with increased macrophage activation. We determined sCD163 levels in 30 children and adolescence with GD compared with 30 healthy controls and assessed the relation to phenotypes, disease severity and complications. Thirty GD patients (10 had type 1 and 20 had type 3) were studied stressing on skeletal, pulmonary or neurological manifestations, enzyme replacement therapy (ERT), hematological profile, plasma chitotriosidase activity, D-dimer and sCD163. Liver and spleen volumes and bone mineral density (BMD) were assessed. sCD163 levels were markedly elevated in patients compared with controls. D-dimer, chitotriosidase activity and sCD163 levels were significantly increased in type 3 GD patients compared with type 1. sCD163 was significantly elevated in GD patients with dysphagia, developmental delay, pulmonary hypertension risk or abnormal BMD (osteopenia/osteoporosis) than those without. GD patients receiving ERT every 2weeks had lower levels than those under ERT for more than 2weeks. sCD163 was positively correlated with age, disease duration, severity score index, D-dimer and chitotriosidase activity. The cutoff value of sCD163 at 9400ng/mL could differentiate GD patients with and without pulmonary hypertension risk with a sensitivity of 90% and specificity of 95%. sCD163 is a biomarker for the clinical assessment of macrophage proliferation and activity that would help in risk prediction of bone and lung involvement and monitoring treatment response.

Effect of factors produced by the placenta on cytokine secretion by THP-1 cells cultured on a 3D scaffold.

We compared the effects of soluble products from the placenta obtained from women with normal pregnancy and pregnancy complicated by preeclampsia on cytokine secretion by THP-1 cells cultured on a 3D Matrigel scaffold. In the presence of soluble products from all placentas, the cells actively secreted IL-8, MCP-1, and soluble forms of CD14, TNFRI, and TNFRII receptors. Secretion of VEGF was below the spontaneous level. Secretion of IL-6 by THP-1 cells after incubation with soluble products of the placentas obtained during weeks 9-11 of physiological pregnancy and 38-39 of pregnancy complicated by preeclampsia surpassed the spontaneous level. In the presence of soluble factors of trimester I placentas, secretion of IL-6 and soluble form of TNFRI receptor was higher than in the presence of trimester III placental factors. Secretion of IL-6 by THP-1 cells was higher, while secretion of soluble TNFRII receptor was lower in the presence of placentas from women with preeclampsia in comparison with physiological pregnancy.

Production and characterization of human soluble CD83 fused with the fragment crystallizable region of human IgG1 in Pichia pastoris

The cell surface protein CD83 belongs to the immunoglobulin superfamily and is highly expressed on mature dendritic cells. The soluble form of CD83, sCD83, is a potential immune suppressor. In a previous study, recombinant soluble CD83 was expressed in Escherichia coli, resulting in a lack of functional glycosylation. Although eukaryotic cell systems for producing sCD83 offer the advantages of protein processing, folding, and posttranslational modification, these systems are complicated, expensive, and produce low levels of protein. To obtain more efficient expression of sCD83, we expressed human sCD83 fused with fragment crystallizable region of human IgG1 (hIgG1 Fc) in Pichia pastoris. Under the optimal conditions (time of induction, 48 h; inoculum density (OD600), 80; concentration of methanol, 3.0 %; pH 7.0-8.0; concentration of casamino acid, 5.0 %), the purified human sCD83-hIgG1 Fc (hsCD83-Ig) fusion protein existed as dimers at 25-30 mg/L culture. Treatment with PNGase F showed that purified hsCD83-Ig was modified by N-linked glycosylation. Moreover, the hsCD83-Ig expressed in the P. pastoris system could suppress lymphocyte proliferation in ConA-stimulated and one-way mixed lymphocyte reaction systems. Thus, hsCD83-Ig expressed in P. pastoris is functional and may be used in experimental therapies for graft rejection, graft-versus-host disease, and autoimmune diseases.

Bifunctional CD4–DC-SIGN Fusion Proteins Demonstrate Enhanced Avidity to gp120 and Inhibit HIV-1 Infection and Dissemination

Early stages of mucosal infection are potential targets for HIV-1 prevention. CD4 is the primary receptor in HIV-1 infection whereas DC-SIGN likely plays an important role in HIV-1 dissemination, particularly during sexual transmission. To test the hypothesis that an inhibitor simultaneously targeting both CD4 and DC-SIGN binding sites on gp120 may provide a potent anti-HIV strategy, we designed constructs by fusing the extracellular CD4 and DC-SIGN domains together with varied arrangements of the lengths of CD4, DC-SIGN and the linker. We expressed, purified and characterized a series of soluble CD4-linker-DC-SIGN (CLD) fusion proteins. Several CLDs, composed of a longer linker and an extra neck domain of DC-SIGN, had enhanced affinity for gp120 as evidenced by molecular-interaction analysis. Furthermore, such CLDs exhibited significantly enhanced neutralization activity against both laboratory-adapted and primary HIV-1 isolates. Moreover, CLDs efficiently inhibited HIV-1 infection in trans via a DC-SIGN-expressing cell line and primary human dendritic cells. This was further strengthened by the results from the human cervical explant model, showing that CLDs potently prevented both localized and disseminated infections. This is the first time that soluble DC-SIGN-based bifunctional proteins have demonstrated anti-HIV potency. Our study provides proof of the concept that targeting both CD4 and DC-SIGN binding sites on gp120 represents a novel antiviral strategy. Given that DC-SIGN binding to gp120 increases exposure of the CD4 binding site and that the soluble forms of CD4 and DC-SIGN occur in vivo, further improvement of CLDs may render them potentially useful in prophylaxis or therapeutics.

Abstract 45: The clinical significance of CD163 in patients with hepatocellular carcinoma who underwent curative resection

Abstract Background We have found that the abundance of peritumoral CD68+ macrophages was associated with patients’ prognosis after curative resection of hepatocellular carcinoma (HCC). However, the role of the pro-tumoral or tumoricidal macrophages is still not clear. Methods In this study, the clinical significance of immunostaining of CD163, a marker of alternatively activated macrophages (M2), in tumor and peritumoral liver tissue from a cohort of 295 Chinese HCC patients who underwent curative resection was evaluated and compared with that of the immunostaining of CD68. The clinical significance of soluble form of CD163 (sCD163) in peripheral blood was also evaluated in another cohort of 107 HCC patients. Results The count of CD163+ cells was well correlated with and much higher than that of CD68+ cells in both tumors and peritumoral liver tissues respectively, which was consistent with the observation from immunostaining by CD68 or CD163 antibody on the consecutive sections. Patients with a higher count of peritumoral CD68+ cells was associated with poor recurrence-free survival and overall survival (P = 0.004 and, P = 0.001, respectively), whereas the counts of tumor and peritumoral CD163+ cells did not. Plasma sCD163 level was associated with active hepatitis-related factors (e.g. serum alanine aminotransferase, serum aspartate aminotransferase, γ-glutamyl transpeptidase and serum alkaline phosphatase). Conclusions CD163+ cell count is of limited significance to predict patients’ prognosis in HCC. Plasma sCD163 was more likely a factor related with active hepatitis rather than tumor related features. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 45. doi:1538-7445.AM2012-45

A Peptide of CD14 Protects Human Lymphocytes from Gliotoxin-Induced Apoptosis

CD14 is a 56 Kd glycoprotein typically present on myeloid cells and originally implicated in innate immunity and pattern recognition. The possible involvement of its membrane bound form with the clearance of apoptotic cells and its recently demonstrated expression by non-myeloid cells, make this fascinating molecule a target for more research and possible therapeutic use. The objective of this study was to assess the possible anti apoptotic effect of the soluble form of CD14, on human lymphocytes and to delineate the fragment, from within the protein that may be mediating that activity. Human peripheral blood lymphocytes were cultured in vitro and induced for apoptosis with gliotoxin, with or without the addition of rhCD14 or CD14 peptide. As controls, we used lymphocyte cell lines such as Jurkat, NK-YTS and also normal peripheral blood neutrophils. We demonstrate that human soluble CD14 is capable of protecting human lymphocytes from gliotoxin- induced apoptosis in vitro. It is not capable of protecting gliotoxin-treated apoptotic Jurkat or NK-YTS cells. Moreover, we reveal that a fragment of the protein, a peptide that is recognized by the MO2 monoclonal anti-CD14 antibody, retains this protective effect, although with a lower efficiency. We have previously shown that the MO2 epitope was found naturally inside human lymphocytes. Here, we demonstrate that the MO2 peptide can penetrate lymphocytes in human peripheral blood mononuclear cells incubated in vitro. The peptide does not penetrate Jurkat or NK-YTS cells and it does not protect them from apoptosis. In addition, peripheral blood neutrophils, in which the peptide penetration was much better than in lymphocytes, could not be protected by this peptide from their spontaneous apoptosis in vitro.Our data thus suggest that circulating CD14 may play an important role in the prevention of apoptosis of lymphocytes and that a specific region from within the molecule is involved in this activity.

The function of soluble form of CD163 in severe infection and sepsis

CD163 is one of transmembrane glycoproteins expressed only in activated monocyte-macrophage cell membrane, which acts as a marker of activated macrophages. In sepsis, CD163 activates the intracellular signal transduction pathways in macrophages,regulates TNF-α, IL-10 and IL-6 expression, have antiinflammatory and antioxidant effects in the inflammatory process. Soluble CD163 (sCD163) is a soluble form of CD163 ,which could play anti-inflammatory and immunoregulatory effects by inhibiting T cells proliferation and activation. Serum concentration of sCD163 may be highly increased when severe infection. Detection of serum sCD163 is helpful to diagnose sepsis,and to evaluate the prognosis of severe infection and sepsis. Key words: Severe infection; Sepsis; Soluble CD163