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PubMed1998

Down-regulation of surface monocyte lipopolysaccharide-receptor CD14 in patients on cardiopulmonary bypass undergoing aorta-coronary bypass operation.

OBJECTIVES: Major operative trauma like aorta-coronary bypass operation may lead to postoperative immunodisturbance, putting the patient at an increased risk for infection and sepsis. The monocyte/macrophage system and the endotoxin receptor CD14 are important in the early recognition and elimination of invading bacteria. The aim of this study was to analyze changes in membrane-associated CD14 and soluble CD14 during and after cardiac involving cardiopulmonary bypass. METHODS: We studied numbers of leukocytes, monocytes, and monocyte subpopulations, expression of monocyte membrane-associated CD14 and plasma levels of soluble CD14 in 10 patients (63 +/- 8 years of age), who underwent elective cardiopulmonary bypass. RESULTS: Cardiopulmonary bypass induced marked postoperative monocytosis, which was maximal 20 hours after the operation (485 +/- 242 cells/microl before, 1080 +/- 264 cells/microl 20 hours after surgery). Expression of membrane-associated CD14 on classical CD14++ monocytes decreased significantly by 40%, reaching a nadir 20 hours after surgery (p < 0.05). At the time of maximal membrane-associated CD14 suppression, the levels of soluble CD14 measured by enzyme-linked immunosorbent assay were clearly increased (3.2 +/- 1.0 microg/ml before versus 5.6 +/- 1.0 microg/ml 20 hours after, p < 0.001). No significant change of the percentage of small (alpha) and large (beta) forms of soluble CD14 was found. CONCLUSIONS: Cardiopulmonary bypass leads to reduced membrane-associated CD14 expression on peripheral blood monocytes and increased levels of soluble CD14 through shedding or secretion of membrane-associated CD14 from the cell surface. These findings indicate that bypass is associated with significant monocyte activation.

Blotting, Western↗

PubMed1993

Isolation and characterization of human peripheral blood dendritic cells.

Dendritic cells (DC) are potent APC that can be purified from cultured peripheral blood non-T cells. Because no specific cell surface marker has been found, the lineage of DC remains obscure. The purpose of these studies was to determine the circulating blood cells that could give rise to functional human DC. DC were enriched when purified by standard techniques from non-T cells that were treated with L-leucyl-L-leucine methyl ester, known to be toxic to monocytes and cytolytic cells. To determine whether monocytes or B cells could give rise to DC, fresh non-T cells were sorted into CD14+ monocytes, CD19+ B cells, and CD14- and CD19- cells. Although there was some enrichment for APC function by cultured nonadherent CD14- or CD19- cells, a marked enrichment for cells with dendritic morphology and potent APC function was found in the population that was sorted by the absence of expression of CD14, CD19, CD3, and CD16. More than 90% of the CD14-CD19-CD16-CD3- sorted cells, and of control DC, expressed the myeloid markers CD13 and CD33. Therefore, fresh non-T cells were sorted based on the expression of these myeloid markers. In comparison with CD33-CD14- B cells, some of the CD33+ cells expressed CD14 dimly. However, they were easily distinguished from monocytes, which intensely expressed CD14. CD33+CD14dim cells developed dendritic processes and were more potent APC than control DC, CD33+CD14+, or CD33-CD14- cells. Although freshly isolated CD33+CD14dim DC expressed a number of cell surface molecules also expressed by CD14+ monocytes, they demonstrated lower levels of lysosomal enzymes and a lack of FcR-mediated phagocytosis in comparison with monocytes. Differentiation of morphology and phenotype of CD33+CD14dim cells occurred within 6 to 36 h in culture. However, the CD33+CD14dim cells could effectively function as APC without prolonged preincubation to develop dendritic morphology. These data indicate that human blood DC arise from precursors that express the myeloid lineage markers CD13 and CD33, but are functionally distinct from classic CD14+ monocytes.

Antigen-Presenting Cells↗

PubMed1989

Mononuclear cells from human lung parenchyma support antigen-induced T lymphocyte proliferation.

We have previously demonstrated that there is a subpopulation of loosely adherent pulmonary mononuclear cells that can be isolated from minced and enzyme-digested lung tissue with a potent capacity to stimulate allogeneic T lymphocyte proliferation. We now demonstrate that these cells are also capable of stimulating an autologous mixed leukocyte reaction (AMLR) and presenting antigen to autologous T lymphocytes. These loosely adherent mononuclear cells (LAM) were more effective than either alveolar macrophages or monocytes as antigen-presenting cells. Depletion of phagocytic or Fc receptor-positive cells from the LAM population enhanced the stimulation of an reaction AMLR while preserving antigen-induced T lymphocyte proliferation. These results indicate that there are nonphagocytic, Fc receptor-negative accessory cells in human lung parenchyma capable of activating resting T cells in an AMLR and supporting antigen-specific T lymphocyte proliferation. The identity of these cells is uncertain, but the data strongly suggest that the cell is not a classical monocyte-derived macrophage. These antigen-presenting cells may be critical in the initiation of immune responses within the lung.

Antigens, Viral↗

PubMed1997

Mesenchymal cells stimulate human intestinal intraepithelial lymphocytes.

BACKGROUND & AIMS: Intraepithelial lymphocytes (IELs) from human intestinal mucosa proliferate minimally to T-cell stimuli. Optimal growth may depend on factors that are missing in vitro, such as accessory cells. The aim of this study was to determine whether mesenchymal cells costimulate IELs. METHODS: IELs were isolated from human jejunum and cultured with fibroblasts or smooth muscle cells (mesenchymal cell models for mucosal myofibroblasts) and various T-cell stimuli. Proliferation was determined by [3H]thymidine incorporation, and interleukin 2 (IL-2) production was measured by enzyme-linked immunosorbent assay. Surface molecules were detected by immunofluorescence and flow cytometry. RESULTS: The proliferative responses of IELs to mitogen (phytohemagglutinin), superantigen (staphylococcal enterotoxin B), or anti-CD3 antibody were increased greatly by coculture with mesenchymal cells, while only slightly by peripheral-blood monocytes, the classical antigen-presenting cells. IL-2 production and receptor expression also increased. Mesenchymal cell costimulation of IEL growth required direct contact between the two cell types and was partly dependent on the integrin alpha4beta1 (very late activation 4[VLA-4]) and major histocompatibility complex (MHC) class I, as their respective antibodies blocked the effect. The surface molecules B7 (CD80), CD2, and MHC class II were not involved. CONCLUSIONS: Optimal IEL growth depends on their contact with mesenchymal cells, an interaction that is mediated by VLA-4 and MHC class I. In mucosal immunity, basement membrane myofibroblasts likely serve this role.

CD8-Positive T-Lymphocytes↗

PubMed1999

CD4+ CD56+ cutaneous neoplasms: a distinct hematological entity? Groupe Français d'Etude des Lymphomes Cutanés (GFELC).

We report seven cases of particular cutaneous tumors selected from the register of the French Study Group on Cutaneous Lymphomas. The patients (three men, four women) were aged 37-86 years. They initially presented with cutaneous nodules or papules. Three cases presented with regional lymph nodes. Stagings were negative, except for one patient with bone marrow involvement. Histological features were relevant with pleomorphic medium T-cell lymphoma, but these cells exhibited a distinguishing phenotype. They were positive for CD4, CD56, and also CD45, CD43, and HLA-DR. All other T-cell and B-cell markers were negative. The myelomonocytic markers (CD13, CD14, CD15, CD33, CD117, myeloperoxidase, and lysozyme) were negative excepted CD68, which was clearly positive in four cases and weakly in two cases. Others natural killer cell markers (CD16, CD57, TiA1, granzyme B), TdT, and CD34 were negative. Polymerase chain reaction studies did not detect any B or T clonal rearrangement. The cytogenetic studies, performed in five cases, showed a del(5q) in two cases. All patients were treated successfully by polychemotherapy, but relapsed quickly in the skin, between 4 and 28 months. Five patients developed bone marrow involvement, with leukemia in three cases, and they died in 5-27 months. One patient died at 17 months with skin progression. The seventh patient is alive at 33 months, with cutaneous progression. The origin of these cells is unclear. Despite expression of CD4 or CD56, we failed to demonstrate a T-cell, natural killer cell origin. However, CD4 and CD56 are not specific for T or natural killer lineages. Although these two markers are also known to be expressed by monocytic cells, classic myeloid antigens were negative. These seven cases, together with other rare similar cases already reported, seem to represent a distinct entity likely developed from hematological precursor cells.

Adult↗

PubMed2006

Migratory fate and differentiation of blood monocyte subsets.

Monocytes are established circulating precursors for tissue macrophages and dendritic cells (DCs). Monocyte-derived macrophages and DCs fulfill critical roles in innate and adaptive immunity during inflammation, and it is believed that monocytes also maintain these populations in peripheral tissues during homeostasis. However, the continuous replenishment of any DC pool by blood monocytes in the steady state remains to be established, and some macrophage populations may be self-renewing in the steady state. Recent identification of mouse monocyte subsets that closely resemble human monocyte subsets has inspired a variety of techniques wherein monocytes can be readily traced in vivo to address these critical questions. There are two major monocyte subsets that vary in chemokine receptor (CCR) and adhesion molecule expression, and in migratory and differentiation properties. In humans, 'classical' CD14+ CD16- monocytes express CCR2, CD64, CD62L, whereas 'non-classical' CD14low CD16+ monocytes lack CCR2. Their counterparts in mice are CCR2+ Gr-1hi and CCR2- Gr-1low monocytes, respectively. Gr-1hi (Ly6Chi) monocytes are recruited to inflammatory sites, e.g. inflamed skin or acutely inflamed peritoneum and give rise to macrophages and DCs in inflammatory or infectious disease models and to epidermal Langerhans cells after skin inflammation. Gr-1low monocytes have been proposed as precursors for steady state DCs, but experimental evidence is as of yet limited. Fortunately, the rate of progress in the study of monocyte fate is rapidly picking up pace, giving rise to the expectation that we will soon know much more about the biology of monocytes in the steady state and inflammation.

Animals↗

PubMed1990

Augmentation of monocyte chemotaxis by 1 alpha,25-dihydroxyvitamin D3. Stimulation of defective migration of AIDS patients.

Preincubation for 20 h with 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) markedly augmented the chemotactic responsiveness of human blood monocytes to the classical chemoattractant, FMLP. A modest enhancement of monocyte spontaneous locomotion in the absence of chemoattractants was also observed. Maximal increase of monocyte migration was observed after pretreatment with 10(-9) M 1,25(OH)2D3 and was detectable at FMLP concentrations ranging from 10(-10) to 10(-7) M. Pretreatment with 1,25(OH)2D3 augmented the number of monocyte high affinity FMLP receptors (1500 +/- 220 and 3800 +/- 300 sites per cell for untreated and 1,25(OH)2D3-pretreated cells, respectively) with no significant changes in Kd values (2 +/- 0.5 nM and 4 +/- 1 nM, for untreated and 1,25(OH)2D3-pretreated monocytes). Enhanced chemotaxis was not restricted to FMLP, because 1,25(OH)2D3-treated monocytes showed enhanced migration also in response to activated C components and chemotactic cytokines. In agreement with previous observations, monocytes from AIDS patients showed defective migration capacity. In vitro exposure to 1,25(OH)2D3 stimulated monocyte migration in all 10 patients examined with considerable quantitative differences among individuals. Regulating the responsiveness of mature monocytes to chemo-attractants, 1,25(OH)2D3, produced systemically or in situ by immunocompetent cells, could play a role in the regulation of the recruitment of monocytes at sites of inflammation, cell-mediated immunity, or bone resorption. The potential of 1,25(OH)2D3 as a restorative agent under conditions of defective phagocyte recruitment deserves further exploration.

Acquired Immunodeficiency Syndrome↗

PubMed1982

Monocyte function in patients with chronic granulomatous disease of childhood.

Adults with chronic granulomatous disease of childhood (CGD) have been described who remain relatively free of infection despite markedly abnormal neutrophil function. Monocyte function in four adults with this mild or atypical CGD syndrome was examined and compared to that of normal controls and to that of two patients with the more severe or classic CGD syndrome. Monocytes from patients with atypical CGD killed 75.7% +/- 2.6% (mean +/- SEM) of ingested organisms at 30 min, while monocytes from the patients with classic CGD killed only 50.3% +/- 4.2% of bacteria (p less than 0.001). The difference in bactericidal activity between atypical CGD monocytes and normal monocytes was relatively small (75.7% +/- 2.6% versus 88.1% +/- 3.7%, respectively) but was statistically significant (p = 0.007). Monocytes from both atypical and classic CGD patients showed markedly impaired oxidative metabolism. Differences in monocyte bactericidal activity may explain why atypical CGD patients have fewer infections than classic CGD patients. The presence of nonoxidative bactericidal mechanisms in atypical CGD monocytes is suggested by the demonstration of bactericidal activity despite severe oxidative metabolic defects.

Blood Bactericidal Activity↗

PubMed2002

Signaling of monocytic differentiation by a non-hypercalcemic analog of vitamin D3, 1,25(OH)2-5,6 trans-16-ene-vitamin D3, involves nuclear vitamin D receptor (nVDR) and non-nVDR-mediated pathways.

Exposure of leukemia cells to the physiologically active form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25D3) normalizes their phenotype to cells that resemble mature monocytes. One of the earliest detectable events in this process is an upregulation of the nuclear receptor for 1,25D3, the vitamin D receptor (nVDR). In contrast, the novel analog of 1,25D3, 1,25-dihydroxy-5,6 trans-16-ene-vitamin D3 (5,6-16D3), which has recently been reported to have low calcium-mobilizing activity in vivo, rapidly induced the expression of CD14, CD11b, and monocyte-specific esterase (MSE), classical markers of the mature monocyte, but upregulated nVDR expression less than 1,25D3. This upregulation was shown to be the result of altered degradation of the nVDR protein, while the levels of nVDR mRNA were constant. Knock-out of nVDR transcriptional activity by a decoy VDRE double-stranded deoxyoligonucleotide, markedly abrogated 1,25D3-induced differentiation, but incompletely inhibited 5,6-16D3-induced differentiation. These findings suggest that the unique ability of 5,6-16D3 to induce cell differentiation but not systemic hypercalcemia, may be due to the activation of pathways which initiate differentiation independently of nVDR.

Antineoplastic Agents↗

PubMed2000

Comparative analysis of CD137 and LPS effects on monocyte activation, survival, and proliferation.

CD137 (ILA/4-1BB), a member of the TNF receptor family, regulates activation, survival and proliferation of primary human monocytes. Here we compare the activities of lipopolysaccharide (LPS), a classical and potent monocyte activator to that of CD137. LPS is a more potent activator of monocytes, as evidenced by a stronger induction of the proinflammatory cytokine IL-8. However, CD137 could further increase maximal cytokine induction by LPS, which points to separate signaling pathways for LPS and CD137. Also, expression of myc was only induced by the combination of CD137 and LPS. Expression of macrophage colony-stimulating factor is induced more potently by CD137, but an additive effect is obtained by the combination of CD137 and LPS. Monocyte/macrophage survival and proliferation is only induced by CD137. LPS counteracts both activities of CD137 via activation induced cell death. While LPS has a role in activation of monocytes in innate immunity, the CD137 receptor/ligand system seems to deliver an activating signal to monocyte in acquired immunity.

Antigens, CD↗

PubMed1993

[The progresses in the determination of blood monocytosis and its perspectives of clinical application in pathology].

Automated cell counters have allowed the reproducible analysis of the 5 leucocyte populations (neutrophils, eosinophils, basophils, lymphocytes and monocytes). Determination of the monocyte count by classical microscopic analysis can be inaccurate. We have compared the automated monocyte count from the coulter STKS (program 1F) with counts obtained by microscopic analysis of 1000 leucocytes and by flow cytometric analysis of cells stained simultaneously with a pan-leucocyte and a monocyte-specific antibody. The values provided by the coulter STKS are sufficiently precise to recommend the routine clinical use of this automated counter.

Female↗

PubMed2005

Dexamethasone, colchicine and iodine-lithium-alpha-dextrin act differentially on the oxidative burst and endotoxin tolerance induction in vitro in patients with Behçet's disease.

Pro-inflammatory activation of innate immune cells, such as macrophages, and neutrophils in patients with Behçet's disease (BD) results in increased production of reactive oxygen species and enhanced adhesion to endothelial cells due to increased expression of adhesion receptors. We investigated the influence of dexamethasone (DEX), colchicine (Col), and iodine-lithium-alpha-dextrin (ILalphaD), during BD, on the respiratory burst of whole blood neutrophils and monocytes, CD11a/CD18 surface expression, monocyte endotoxin tolerance and cytokine synthesis in vitro. In BD patients we observed an increase of the spontaneous, N-formyl-Met-Leu-Phe- and LPS-induced respiratory burst of monocytes and neutrophils as well as up-regulation of neutrophil CD11a/CD18 surface expression. DEX, Col and ILalphaD in vitro differentially affected the stimulus-dependent oxidative burst of BD and caused the down-regulation of CD11a/CD18 surface expression in neutrophils but not monocytes. LPS homologous tolerance induction is not altered in BD. However, DEX and Col increased tolerance to LPS-induced TNF-alpha synthesis. ILalphaD down-regulated N-formyl-Met-Leu-Phe- and LPS-induced oxidative burst and CD14 receptor expression and increased monocyte cross-tolerance to LPS. DEX induced LPS-tolerance by restoring the ratio of INF-gamma and IL-4 production, while Col caused a dramatic increase in IL-4 synthesis by monocytes. DEX, Col and ILalphaD may limit the overwhelming inflammation by differentially affecting the monocyte activation program, shifting them from ''classically" into "alternatively'' activated monocytes and may have important implications for the treatment of BD.

Behcet Syndrome↗

PubMed2005

Pro- and anti-inflammatory substances modulate expression of the leukotriene B4 receptor, BLT1, in human monocytes.

The high-affinity leukotriene B(4) (LTB(4)) receptor, BLT1, is a chemotactic receptor involved in inflammatory responses. In this study, we have explored the regulation of BLT1 expression in human monocytes by pro- and anti-inflammatory cytokines, lipopolysaccharide (LPS), and dexamethasone. We found that proinflammatory mediators, such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha, and LPS, down-regulated expression, whereas the anti-inflammatory cytokine, interleukin-10, and dexamethasone up-regulated BLT1 mRNA expression. The effect of IFN-gamma on BLT1 mRNA expression was rapidly detectable (<4 h) and concentration-dependent (1-50 ng/ml) and seems to be exerted through a block in transcriptional activity. Alterations in mRNA expression were accompanied by changes in BLT1 surface expression, and receptor down-modulation following IFN-gamma stimulation resulted in a diminished chemotactic response to LTB(4). The regulation of BLT1 mRNA and receptor protein expression was similar to the regulation of the monocyte chemoattractant protein-1 chemokine receptor, CC chemokine recptor 2 (CCR2). Flow cytometric analysis of fresh peripheral blood cells revealed that classical (CD14(++)CD16(-)) monocytes express high levels of BLT1 and CCR2 and that both receptors are down-regulated on CD14(+)CD16(+) monocytes. Apart from providing insight into the regulation of BLT1 in human monocytes, our results reveal a parallel expression and regulation of BLT1 and CCR2, which may help to understand monocyte trafficking during pathophysiological conditions.

Chemotaxis↗

PubMed1987

Liposomes expressing IL 1 biological activity.

We determined the activity of IL 1, obtained from various human monocyte subcellular compartments, when associated with liposomes. Soluble IL 1, bound to the outer surface of lyophilized liposomes, stimulated responsive target cells. However, this activity was not preserved when soluble IL 1 was incorporated into the inner chambers of classical liposomes. In contrast, monocyte plasma membranes that exhibited IL 1 activity had the same level of activity when presented on lyophilized liposomes and when incorporated inside the classical liposomes. However, monocyte plasma membranes bound to the outer surface of the liposomes exhibited greater activity than the monocyte membrane IL 1 itself in its soluble form. This suggests that membrane IL 1 is an integral membrane protein, readily integrated into the lipid bilayers. Like soluble IL 1, the expression of IL 1 activity present in the cytosol of activated monocytes was decreased by incorporation into liposomes, but was high and active when presented on lyophilized liposomes. The best artificial cell reconstitution was obtained with lyophilized liposomes in association with monocyte cytosol and plasma membranes. When an unactivated monocyte compartment was mixed with one from an activated monocyte, the signal was equal to that of the activated cell compartment alone. The IL 1 activity of activated cell fractions associated with lyophilized liposomes was determined, and an increase of IL 1 activity for both plasma membranes and cytosol was observed, whereas a decrease of the signal was obtained for the lysosomal compartment. Endoplasmic reticulum showed no IL 1 activity, even after trypsin treatment. The highest activity after trypsin treatment was recovered in the cytosol associated with lyophilized liposomes, suggesting that molecules obtained after this treatment were able to bind tightly to the lipid bilayers.

Cell Compartmentation↗

PubMed2004

Inhibition of Leishmania donovani promastigote DNA topoisomerase I and human monocyte DNA topoisomerases I and II by antimonial drugs and classical antitopoisomerase agents.

We have compared the inhibitor sensitivities of DNA topoisomerase I (TOPI) from Leishmania donovani promastigotes and TOPs I and II of human monocytes using pentavalent and trivalent antimonials (SbV, SbIII) and classical TOP inhibitors. Bis-benzimidazoles (Hoechst-33258 and -33342) were potent inhibitors of both parasite and human TOPI, but Hoechst-33342 was markedly less cytotoxic to promastigotes than to monocytes in vitro. Leishmania donovani was also considerably less sensitive than monocytes to camptothecin, both at enzyme and cellular levels. Sodium stibogluconate (SSG) was the only antimonial to inhibit TOPI, exhibiting a significant (P < 0.05) 3-fold greater potency against the L. donovani enzyme but showed low cytotoxicities against intact promastigotes. The SbV meglumine antimoniate failed to inhibit TOPI and showed negligible cytotoxicities, whereas SbIII drugs were lethal to parasites and monocytes yet poor inhibitors of TOPI. Monocyte TOPII was inhibited by bis-benzimidazoles and insensitive to antimonials and camptothecin. The disparity between the high leishmanicidal activity and low anti-TOPI potency of SbIII indicates that in vivo targeting of L. donovani TOPI by the reductive pathway of antimonial activation is improbable. Nevertheless, the potent direct inhibition of TOPI by SSG and the differential interactions of camptothecin with L. donovani and human TOPI support the possibility of developing parasite-specific derivatives.

Animals↗

PubMed2005

Dendritic cells differentiated in the presence of IFN-{beta} and IL-3 are potent inducers of an antigen-specific CD8+ T cell response.

Dendritic cells (DC) are professional antigen-presenting cells that are used in vaccine approaches to cancer. Classically, mature monocyte-derived DC are generated in vitro in the presence of interleukin (IL)-4, granulocyte macrophage-colony stimulating factor, and inflammatory cytokines (G4-DC). Recently, it has been described that DC can also be generated in the presence of IL-3 and interferon (IFN)-beta and that these DC are efficiently matured using polyriboinosinic polyribocytidylic acid (I3-DC). In this study, a series of in vitro experiments was performed to compare side-by-side I3-DC and G4-DC as vaccine adjuvants. Phenotypic characterization of the DC revealed differences in the expression of the monocyte marker CD14 and the maturation marker CD83. Low expression of CD14 and high expression of CD83 characterized G4-DC, whereas I3-DC displayed intermediate expression of CD14 and CD83. Both types of DC were as potent in the induction of allogeneic T cell proliferation. Upon CD40 ligation, G4-DC produced lower amounts of IFN-alpha and pulmonary and activation-regulated chemokine, similar amounts of IL-6, macrophage-inflammatory protein (MIP)-1alpha, and MIP-1beta, and higher amounts of IL-12 p70, tumor necrosis factor alpha, and MIP-3beta than I3-DC. We further evaluated whether the DC could be frozen/thawed without loss of cell number, viability, phenotype, and function. After freezing/thawing, 56.0% +/- 9.0% of I3-DC and 77.0% +/- 3.0% of G4-DC (n=9) were recovered as viable cells, displaying the same phenotype as their fresh counterparts. Finally, in vitro stimulations showed that fresh and frozen peptide-loaded I3-DC are more potent inducers of Melan-A-specific CD8(+) T cell responses than G4-DC. The antigen-specific T cells were functional as shown in cytotoxicity and IFN-gamma secretion assay.

CD8-Positive T-Lymphocytes↗

PubMed1989

Induction of antibody-dependent cellular cytotoxicity against endothelial cells by renal transplantation.

Antibodies that induce antibody-dependent cellular cytotoxicity (ADCC) of human umbilical-vein endothelial cells (EC) were detected using serum of a renal transplant patient who had experienced a severe vascular rejection episode after receiving an HLA-identical kidney graft from a living-related donor. This reactivity was absent in sera obtained before transplantation. The antibody nature of the reactivity present in the post-transplantation sera was proven by gelfiltration studies, protein A absorption, pepsin-digestion experiments, and incubation with subclass specific monoclonal antibodies; predominantly IgG1 antibodies were found to bind to EC and induce ADCC. The specificity of the antibodies could be shown in panel studies using EC lines of various donors. In order to investigate the clinical relevance and incidence of anti-EC ADCC, we examined whether anti-EC reactivity could be observed in 9 additional renal transplant patients. Sera of 2 of these patients were found positive in the ADCC assay, whereas 20 normal serum donors were negative. ADCC against EC in these patients was not caused by classic antiendothelial-monocyte (EM) antibodies. Using various experimental systems (adherent cell depletion, monoclonal antibody blocking, cold target cell inhibition) it was shown that the natural killer/killer (NK/K) cells present within the peripheral blood mononuclear cell population were responsible for EC lysis. These findings demonstrate that IgG1 antibodies directed against polymorphic non-HLA, non-EM antigens on EC can be induced by renal allotransplantation. Via Fc-receptor interaction with NK/K cells, these antibodies can be responsible for ADCC against EC.

Antibodies, Monoclonal↗

PubMed1992

Acute monocytic leukemia with (8;22)(p11;q13) translocation. Involvement of 8p11 as in classical t(8;16)(p11;p13).

A new case of acute monocytic leukemia observed in a 73-year-old male (ANLLM5) with an unusual t(8;22)(p11;q13) is reported. The blasts did not demonstrate erythrophagocytosis, but the presence of both naphthol-ASD-chloro-acetate esterase and butyrate esterase activities was similar to that seen in cases with t(8;16)(p11;p13). Involvement of the 8p11 region in ANLLM4 and M5 is discussed, being the third most frequent rearrangement in acute leukemia with monocytic components seen at our Center.

Aged↗