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Biomedical subjects

R Andreesen

Publications and source records attributed to R Andreesen.

At least 55 records · Page 3Linked to original sources
PubMed2000

Naive monocytes can trigger transendothelial migration of peripheral blood cells through the induction of endothelial tumour necrosis factor-alpha.

In this manuscript we describe a potentially new mechanism by which unstimulated human monocytes activate endothelial cells (EC) through the secondary induction of endothelial tumour necrosis factor alpha (TNF-alpha). Serum free supernatants (SN) of peripheral blood mononuclear cells (PBMC) strongly induce the expression of intercellular adhesion molecule 1 (ICAM-1, CD54), vascular cell adhesion molecule 1 (VCAM-1, CD106), and endothelial-leukocyte adhesion molecule 1 (ELAM-1, CD62E) on human EC 24 and 4 h post treatment, respectively. Further characterization of the responsible subpopulation revealed the CD14+ monocytes and a monocytic cell line (MM6) to produce an endothelial activating factor (EAF). The EAF also triggers an adhesion and a transendothelial migration (TEM) of peripheral blood cells. Using neutralization with an anti TNF-alpha MoAb MAK195, EAF is not identical with TNF-alpha, but induces the expression of endothelial TNF-alpha, since MAK195 blocked TEM only when coincubated with EC, not with monocytes. Furthermore, intracellular TNF-alpha was significantly upregulated in EC after treatment with SN-MM6. Another evidence for a secondary autocrine mechanism was provided by culturing the EC with a conditioned medium of SN-MM6 treated EC. This conditioned medium induces an adhesion molecule expression and TEM in a similar way to SN-MM6 and can completely be inactivated by anti TNF-alpha. Taken together, these data may have an impact for, e.g. transplantational settings that donor monocytes may trigger an inflammatory response in the absence of further activation signals by eliciting an endogenous TNF-alpha response in the host.

Cell Adhesion↗
PubMed2000

[The ultrasound centre as a medically and economically relevant alternative--a report of the Regensburg experience].

In most medical centres, ultrasonography is performed independently by several departments. In october 1997, the University hospital of Regensburg founded an ultrasound centre, integrating surgical and medical departments as well as the institutes for radiology and nuclear medicine. The aims of this centre were the concentration of organization, machines, financial resources, manpower and know-how, standardized training and quality, and strengthening of interdisciplinary cooperation in clinic, medical education and research. Booking, standardized reports and a joint archiving of reports are assisted by a collective computer system. Most examinations in the centre are performed by three all-day present gastroenterology, surgery and radiology residents who are supported by licensed sonographers of the other departments. Training is standardized, and the certification for ultrasound examinations is acquired after a test with theoretical and practical parts. The integration of various departments in the ultra-sound on-call service has led to significant savings. The pool of ultrasound machines is used jointly, department-specific resources for new machines have been put together. We are convinced that this way of a close interdisciplinary cooperation will result in improvements in quality, utilization of financial resources and clinical research.

Cost-Benefit Analysis↗
PubMed2000

Hsp70 plasma membrane expression on primary tumor biopsy material and bone marrow of leukemic patients.

A tumor-selective cell surface localization of heat shock protein 70 (Hsp70), the major heat-inducible member of the Hsp70 group, correlates with an increased sensitivity to lysis mediated by human natural killer (NK) cells and, therefore, might be of clinical relevance. With the exception of mammary carcinomas, an Hsp70 plasma membrane expression was found on freshly isolated human biopsy material of colorectal, lung, neuronal, and pancreas carcinomas, liver metastases, and leukemic blasts of patients with acute myelogenous leukemia. Since normal tissues and bone marrow of healthy human individuals do not express Hsp70 on the cell surface, Hsp70 can be considered as a tumor-selective structure in vivo. Furthermore, we demonstrate that autologous, Hsp70-positive leukemic blasts can be killed by NK cells stimulated with low doses of interleukin 2 plus recombinant Hsp70 protein.

Adenocarcinoma↗
PubMed1999

The selenoprotein thioredoxin reductase is expressed in peripheral blood monocytes and THP1 human myeloid leukemia cells--regulation by 1,25-dihydroxyvitamin D3 and selenite.

1,25(OH)2 Vitamin D3 (1,25(OH)2D3) and adhesion propagate monocyte differentiation. We identified the selenoprotein thioredoxin reductase (TrxR) as a new molecular target for 1,25(OH)2D3 in monocytes during this process. In THP1 monocytic leukemia cells 1,25(OH)2D3 stimulated TrxR mRNA levels 2-4-fold by 4-8 h and enhanced TrxR activity (60%) (as measured by the dithionitrobenzole-assay) after 24 h, which declined below baseline after 96 h. The addition of 100 nM selenite enhanced (approx. 50%) basal and stimulated enzyme activity in THP1 cells. The relative stimulation by 1,25(OH)2D3 was very similar but peak levels were sustained in THP1 cells up to 48 h. Human peripheral blood monocytes (PBM) of different donors showed very low basal TrxR steady state mRNA levels which were markedly enhanced (as analyzed by Northern blotting) after 4 h of adherence to culture dishes. 1,25(OH)2D3 (100 nM) further stimulated TrxR mRNA expression (4 h, 3-fold). TrxR enzyme activity mirrored the mRNA changes. Basal activity was stimulated approx. 25% by adhesion in culture alone and was further stimulated (approximately 15%) by 1,25(OH)2D3 after 4 h. By 24 h similar results were achieved but the effect of 1,25(OH)2D3 could be seen in the presence of 100 nM selenium only. The expression of TrxR and its regulation by 1,25(OH)2D3 and selenite in monocytes might be important for their induction of differentiation and maintenance of function.

Calcitriol↗
PubMed1999

Transplant characteristics: minimal residual disease and impaired megakaryocytic colony growth as sensitive parameters for predicting relapse in acute myeloid leukemia.

Dose escalation during consolidation therapy of de novo AML, including myeloablative chemotherapy supported with autologous peripheral blood stem cell transplantation (aPBSCT), continuously improved outcome. Therefore, quality control of transplants is getting increasing interest. We studied leukapheresis products (LPs), consecutively collected during postremission treatment of 20 patients with de novo AML for minimal residual disease (MRD) by 5-parametric flow cytometry and for myelodysplasia (MDS)-associated alterations by paired lineage-selected colony assays for colony-forming units-megakaryocytes (CFU-mega) and burst-granulocytes-monocytes colony-forming units (CFU) to evaluate the predictive value of these transplant-associated parameters on outcome. We defined the leukemia-associated immunophenotype at diagnosis and studied the impact of MRD detection in LPs collected after double induction with TAD (thioguanine, daunorubicin, cytarabine) and HAM (mitoxantrone, high-dose cytarabine, n=18 patients) and TAD consolidation treatment (n=20 patients) on outcome after aPBSCT. The level of MRD in the transplants correlated with the relapse-free survival (RFS) using a cut-off level of 1 x 10(-3) residual leukemic cells. The median RFS was 6 months for the group with > or = 1 x 10(-3) residual leukemic cells and has not been reached in the group with low MRD levels (< 1 x 10(-3)). By using the same cut-off level a weak correlation could also be demonstrated between MRD in the pregraft bone marrow and RFS (P = 0.04). Quantitatively abnormal megakaryocytic colony growth in the back-up LPs collected after double induction and in the transplant LPs was characterized by the ratio CFU-mega/CFU. In the group of relapsing patients the ratio CFU-mega/CFU was significantly lower than in the group of patients with CCR (P = 0.004), both in the back-ups and in the transplants. All patients with CFU-mega/CFU ratios < 0.12 relapsed, five of seven patients developed MDS before progressing to full leukemic relapse. Using the optimized cut-off level for the ratio CFU-mega/CFU (< vs > or = 0.12), seven of 10 relapsing patients (70%) could be identified to be at risk of relapse, whereas MRD in the transplants identified only 50% of the relapses and MRD in the pregraft bone marrow 25%. In conclusion, the study could identify two pretransplant risk factors predicting relapse in patients with AML receiving aPBSCT in first CR: MRD in transplants as well as MDS-like alterations within the transplants. These results may have multifold implications on the design of risk-adapted chemotherapy as well as on purging techniques and may contribute to a better understanding of leukemogenesis.

Acute Disease↗
PubMed1999

Granulocyte-macrophage colony-stimulating factor modulates lipopolysaccharide (LPS)-binding and LPS-response of human macrophages: inverse regulation of tumour necrosis factor-alpha and interleukin-10.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a well-known stimulus for the activation, differentiation and survival of monocytes (MO). Up to now most investigations focused on the short-term effects of GM-CSF. In this study we investigated the effects of GM-CSF on the long-term differentiation of human MO in the presence of serum. We found that MO-derived macrophages (Mphi) cultured with serum plus GM-CSF (GM-Mphi) were different from control Mphi (SER-Mphi) in terms of lipopolysaccharide (LPS)-stimulated cytokine release: GM-Mphi showed an increased tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production, especially at lower LPS concentrations, but the secretion of IL-10 was diminished. In addition, GM-Mphi secreted TNF-alpha but not IL-6 and IL-10, spontaneously. The spontaneous TNF-alpha production was not due to LPS contamination as it could not be blocked by anti-CD14 antibody. Flow cytometry revealed, however, that the receptor for LPS, CD14, was up-regulated on GM-Mphi and those Mphi released twice as much soluble CD14 into the supernatant as compared with SER-Mphi. The higher CD14 expression also resulted in an enhanced LPS-binding capacity of GM-Mphi. Furthermore, the LPS-response of GM-Mphi could only be blocked by about fourfold higher concentration of anti-CD14 antibody compared with SER-Mphi. In summary, GM-CSF promotes the generation of a pro-inflammatory type of Mphi in two different ways: first, the down-regulation of autocrine IL-10 production increases the release of cytokines such as IL-6 and TNF-alpha and second, the up-regulation of membrane and soluble CD14 expression leads to a higher sensitivity towards LPS-stimulation.

Antibodies, Monoclonal↗
PubMed1998

Cytokine repertoire during maturation of monocytes to macrophages within spheroids of malignant and non-malignant urothelial cell lines.

Terminal maturation of human blood monocytes to macrophages (MAC) in vivo is believed to be important for the morphology, antigen expression and functional activity of the resulting MAC population. This process is modulated by the specific tissue micro-environment to which blood monocytes migrate upon leaving the vasculature. Tumor-associated macrophages (TAM) are a special type of MAC, and little is known about the modulating capacity of the tumor environment on monocyte-to-MAC differentiation. By co-culturing 3-dimensional multicellular spheroids (MCS) of the urothelial-bladder-carcinoma cell lines J82 and RT4 with human monocytes/MAC we generated TAM in vitro. For comparison, monocytes/MAC were co-cultured with the non-tumorigenic urothelial cell line HCV29. The effects on monocyte differentiation were analyzed, particularly with respect to cytokine release. Monocyte maturation was modulated within the tumor spheroid dependent upon the tumor cell type. Monocytes co-cultured with MCS of the poorly differentiated J82 carcinoma spontaneously produced high amounts of IL-1beta and IL-6, but only low amounts of TNF-alpha, which could be further increased by the addition of LPS. This cytokine pattern is characteristic for monocytes and remained constant for up to 8 days in J82-MCS co-cultures. However, in RT4-MCS and HCV29-MCS co-cultures, the initial cytokine pattern changed and after 8 days corresponded well to that of MAC differentiated in vitro without tumor contact. In addition to functional parameters, we analyzed the morphology of J82-MCS-TAM and found that they displayed a monocyte-like morphology. Our data indicate that (1) tumor cells can influence monocyte-to-MAC differentiation, giving rise to TAM with monocyte-specific phenotypic properties; and (2) this capacity is dependent on the type of tumor cell.

Cell Differentiation↗
PubMed1998

Restricted HIV type 1 replication under serum-free culture conditions in human monocyte-derived macrophages.

Monocytes (MOs) and macrophages (MACs) are well-known targets for HIV-1 infection. Even though the virus load is contributed mainly to lymphocytes during the asymptomatic phase of infection, the expression of HIV-1 in MO/MACs seems to be important for the course of the disease. To establish a model for restricted HIV-1 expression in MACs in vitro, we cultured MO-derived MACs under different culture conditions and analyzed their susceptibility to HIV-1 infection as well as their capacity for virus replication in vitro. MACs cultured under serum-free conditions with M-CSF (M-MACs) remain viable and functionally active as assessed by the analysis of cytokine production. In addition, the levels of CD4, CD14, CCR5, and HLA-DR expression are comparable to those of serum-derived MACs (SER-MACs). However, serum-free MACs were less susceptible to HIV-1 infection, with only 9.5+/-4.5% (mean+/-SEM) of all cells being p24 antigen positive on day 22 as compared with 51+/-9% under serum conditions (p < 0.005). Reverse transcriptase (RT) activity in the culture supernatant of M-MACs was always about 100-fold lower than that of SER-MACs even when comparable amounts of cells were infected. The addition of serum to serum-free cultures increased the percentage of HIV-1 p24 antigen-positive cells (21+/-8% positive cells on day 22) and increased the RT activity, indicating that serum factors could be important for HIV-1 replication in MACs. Therefore we also switched SER-MACs to serum-free culture conditions and found a sharp decrease in RT activity. However, the RT level could always be rescued by the addition of serum, even after a long serum-free culture period. This effect was dependent on the serum concentration added, with as little as 0.1% serum being effective in reestablishing viral production as measured by RT activity. In conclusion, we show that serum has an important role in the replication of HIV-1 in MACs. Our results suggest that besides the role of CD4 and CCR5 other microenvironmental factors, e.g., growth factors, cytokines, or hormones, which are not provided by the target cell itself, are involved in the regulation of MAC infection and of replication by HIV-1.

Cell Culture Techniques↗
PubMed1998

Regulation of cellular retinoic acid binding protein (CRABP II) during human monocyte differentiation in vitro.

Cellular retinoic acid binding proteins (CRABP) are low molecular weight proteins whose precise function remains unknown. They bind retinoids and may thereby modulate the intracellular steady-state concentration of retinoids. Whereas CRABP I is ubiquitously expressed, CRABP II is mainly detected in various cell types of the skin. By representative difference analysis we found that CRABP II is also strongly expressed in human monocyte-derived macrophages (MAC) but not in freshly isolated monocytes (MO). The CRABP II mRNA was gradually upregulated during differentiation from MO to MAC in the presence of 2% serum. Adherence, which is important for MO differentiation, induced CRABP II expression, but the addition of 10(-7) M retinoic acid inhibited the upregulation of CRABP II expression during MO/MAC differentiation. As MO can differentiate along the classical pathway not only to MAC but also to dendritic cells we analyzed the expression of CRABP II in MO-derived dendritic cells cultured with 10% FCS, IL-4, and GM-CSF. In contrast to MAC, MO-derived dendritic cells showed an extremely low expression of CRABP II. From these results we conclude (1) that the availability and the metabolism of retinoids may be different in MAC compared to MO and dendritic cells and (2) that this may influence differentiation and activation of those cells.

Cell Adhesion↗
PubMed1998

Individual cell analysis of the cytokine repertoire in human immunodeficiency virus-1-infected monocytes/macrophages by a combination of immunocytochemistry and in situ hybridization.

The expression of many cytokines is dysregulated in individuals infected with the human immunodeficiency virus-1 (HIV-1). To determine the effects of HIV-1 infection on cytokine expression in individual cells (at the single cell level), we investigated the intracellular levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-6, and IL-8) and hematopoietic growth factors (granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF]) in monocyte-derived macrophages, mock-infected, or infected with HIV-1 by immunocytochemical staining for cytokine protein and compared this with secreted cytokine levels as determined by specific enzyme-linked immunosorbent assay (ELISA). No difference in the frequency or intensity of cell-associated immunocytochemical cytokine staining could be observed between HIV-1 and mock-infected cells even though the level of secreted proinflammatory cytokines increased and the hematopoietic growth factors decreased in HIV-1-infected cultures. Furthermore, equal expression of cytokine mRNA was observed in all cells in the culture regardless of whether the cells were productively infected with HIV-1 as determined by double-labelling immunocytochemical staining for HIV-1 p24 antigen and in situ hybridization for cytokine mRNA expression. These results indicate that HIV-1 infection results in dysregulation of intracellular cytokine mRNA expression and cytokine secretion not only in HIV-1-infected cells, but also through an indirect way(s) affecting cells not producing virus.

Cells, Cultured↗
PubMed1998

Retinoic acid inhibits monocyte to macrophage survival and differentiation.

Vitamin A metabolites are potent differentiation-inducing agents for myelomonocytic cell lines in vitro and are successfully used for the treatment of patients with acute promyelocytic leukemia. However, little is known about the effects of vitamin A on normal hematopoietic cells. Therefore, we investigated the effect of vitamin A on differentiation and activation of human blood monocytes (MO). Culturing MO for up to 4 days with 9-cis retinoic acid (RA) and all-trans RA but not retinol reduced MO survival, with the remaining cells being morphologically comparable to control cells. Because macrophage colony-stimulating factor (M-CSF) is a well-known survival factor for MO, we measured the M-CSF content of MO culture supernatants using enzyme-linked immunosorbent assay and found that RA suppressed the constitutive secretion of M-CSF. Northern analysis showed that the M-CSF mRNA expression was only slightly reduced by RA treatment, suggesting regulation on the posttranscriptional level. In contrast to MO, M-CSF secretion by MO-derived macrophages (MAC) was not altered by RA, suggesting a differentiation-dependent switch in the responsiveness of MO/MAC to RA. Because M-CSF is not only a survival-promoting but also a differentiation-promoting factor for myeloid cells, we analyzed the effect of RA on MO to MAC maturation. RA suppressed the expression of the maturation-associated antigen carboxypeptidase M (CPM)/MAX.1 at both the protein and mRNA levels and modulated the lipopolysaccharide-stimulated cytokine secretion of MO/MAC. The addition of exogenous M-CSF to RA-containing MO cultures fails to overcome the RA-induced inhibition of MO differentiation. However, the survival rate was improved by exogenous M-CSF. We conclude that RA acts via two different mechanisms on monocyte survival and differentiation: posttranscriptionally by controlling M-CSF secretion, which decreases MO survival, and transcriptionally regulating the expression of differentiation-associated genes. The regulation of M-CSF production may contribute to the antileukemic effect of RA in vivo by reducing autocrine M-CSF production by leukemic cells.

Cell Differentiation↗
PubMed1998

CD137 (ILA/4-1BB), a member of the TNF receptor family, induces monocyte activation via bidirectional signaling.

CD137 (ILA/4-1BB), a member of the TNF receptor family, was shown previously to inhibit proliferation and to induce apoptosis in T lymphocytes. In this study, we identify CD137 as a novel and potent monocyte activation factor. CD137 protein induces expression of IL-6, IL-8, and TNF-alpha, and inhibits expression of IL-10. Furthermore, CD137 differentially regulates expression of cell surface receptors. It induces expression of ICAM and reduces expression of FcgammaRIII, while levels of HLA-DR remain unchanged. CD137 also promotes adherence of monocytes. These effects of CD137 require immobilization of CD137 protein, indicating that they are mediated by cross-linking of a corresponding ligand/coreceptor expressed on monocytes.

Antigens, CD↗
PubMed1998

[Symptomatic leukemic infiltration of the lung in acute myeloid leukemia].

HISTORY: A 70-year-old woman was admitted with the suspected diagnosis of acute leukaemia. She had complained of decreased physical capacity, nonproductive cough and dyspnoea. INVESTIGATIONS: The blood picture showed leukocytosis of 46/nl, anaemia (haemoglobin 8.8 g/dl) and thrombocytopenia (25 platelets/nl). Differential white count: 10% blast cells, 43% monocytes. Bone marrow smear revealed acute monocytic leukaemia. The chest radiogram showed increased interstitial markings and lung function tests indicated moderate restriction. TREATMENT AND COURSE: The atypical pneumonia was treated with erythromycin, but the respiratory functions deteriorated further within 2 days. Cytostatic treatment had been started on the second hospital day, but the patient died a few hours later in respiratory failure. Autopsy revealed numerous alveolar infiltrates by immature myeloid cells. CONCLUSION: In patients with acute leukaemia and respiratory symptoms, pulmonary involvement should be included in the differential diagnosis and, if present, chemotherapy immediately begun.

Aged↗
PubMed1998

Platelets induce monocyte differentiation in serum-free coculture.

Terminal maturation of blood monocytes (MO) in vitro and in vivo into macrophages (MAC) occurs as a result of interactions with various cell types. To characterize some of the cell-cell connections that may be important for MO differentiation we cocultured human MO with lymphocytes and/or with platelets. We found that intact platelets strongly promoted MO maturation under serum-free conditions as evident from the expression of differentiation-dependent antigens and morphology. To further characterize the differentiation-inducing component(s) we prepared membrane and cytosol fractions of platelets. Both fractions could induce MO maturation, comparable to intact platelets. Further centrifugation of the cytosolic fraction revealed that only the pellet of ultracentrifugation, e.g., membrane fragments, could induce MO differentiation. Digestion with either trypsin or neuraminidase could only partially inhibit this effect. The same was true for heat-treated fractions, indicating that this platelet-derived differentiation stimulus is not solely an intact protein. Next we prepared protein and lipid fractions of platelets. Treatment of MO with platelet proteins or platelet lipids clearly showed that only the lipid components were able to induce MO maturation. We propose components present in the lipid fraction of platelet membranes as possible inducers of MO maturation in vitro.

Antibodies↗
PubMed1998

Adoptive immunotherapy of cancer using monocyte-derived macrophages: rationale, current status, and perspectives.

Adoptive transfer of host defense cells may be able to correct an otherwise defective generation of competent immune cells in patients with cancer. Ex vivo-grown cytotoxic macrophages (MAC) able to recognize and destroy tumor cells but not normal cells are effective in murine models of metastasizing tumors. After the development of large-scale technology to generate MAC in vitro from blood monocytes (MO), clinical trials in cancer patients have proven the feasibility and safety of infusing >3 x 10(9) autologous MO-derived MAC activated by interferon-gamma or lipopolysaccharide. Various modalities of adoptive immunotherapy with human MAC have been realized: routes of application used were intravenous, intraperitoneal, intrapleural, and through selective hepatic artery perfusion. In addition, MAC have been generated from MO collected after granulyte-macrophage colony-stimulating factor treatment in vivo. Biodistribution studies using 111indium-labeled cells have revealed localization of MAC to sites of bulk tumor growth on regional infusion as well as to liver metastases on systemic application. Malignant ascites disappeared in about 50% of patients after intraperitoneal treatment, yet no other evidence of therapeutic efficacy of MAC could be demonstrated. Further advances of adoptive transfer of MO-derived cells are developed with emphasis on the generation of antigen-presenting cells primed in vitro with tumor cells or specific peptides.

Animals↗
PubMed1998

Phase I trial of adoptive immunotherapy of cancer patients using monocyte-derived macrophages activated with interferon gamma and lipopolysaccharide.

Cells of the monocyte/macrophage lineage have shown antitumor activity in vitro and in murine models after activation with interferon (IFN) gamma. In vitro data suggest an additional effect on macrophage antitumor activity when IFN gamma is combined with endotoxin (lipopolysaccharides; LPS). In this study we treated nine cancer patients with a total of 62 MAK infusion cycles with autologous macrophages given intravenously (i.v.) after in vitro activation with IFN gamma and LPS. Low-grade fever (WHO I/II) was the commonest side-effect. Chills, nausea, and headache were noted when the number of transfused macrophages exceeded 2 x 10(8). One WHO IV toxicity occurred, consisting of hypotension after transfer of 3 x 10(8) cells, defining this dose as the maximum cell number tolerated. After pretreatment with ibuprofen, however, the maximum cell number could be increased without reaching dose-limiting toxicity. The highest number of cells reinfused was 15 x 10(8). Circulating interleukin(IL)-6 increased in a dose-dependent manner as did IL-1 receptor antagonist (IL-1RA) and IL-8. Tumor response consisted of one case of stable disease (12 weeks) in a patient with formerly progressing colorectal cancer and progressive diseases in eight patients. This study indicates that reinfusion of autologous LPS-activated macrophages upon pretreatment with ibuprofen is feasible and tolerated without major side-effects.

Antithrombins↗
PubMed1998

Comparative analysis of dendritic cells derived from blood monocytes or CD34+ hematopoietic progenitor cells.

In human tissues different populations of dendritic cells (DC) emerge from hematopoietic progenitor cells (HPC) in the bone marrow, with the intermediate steps of differentiation not being completely understood. In vitro, DC can be directly obtained from HPC or from blood monocytes (MO) cultured in the presence of GM-CSF and additional cytokines. We compared the antigenic profile of DC derived from either MO or HPC and studied their capacity to stimulate naive lymphocytes (LY) in the allogeneic mixed lymphocyte reaction. Both types of DC expressed high levels of CD1a, MHC class II, CD80, CD86 and CD40 and were potent stimulators of LY proliferation. DC of HPC origin, though, induced a stronger mixed lymphocyte reaction than MO-derived DC and showed a slightly higher average expression of costimulatory antigens. Low-level expression of CD14 did not negatively correlate with DC function on DC stimulated with lipopolysaccharide and was even slightly higher expressed on DC differentiating from HPC than on DC from CD14+ MO.

Antigen Presentation↗