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C D Dijkstra

Publications and source records attributed to C D Dijkstra.

At least 37 records · Page 2Linked to original sources
PubMed2001

Rat macrophages: membrane glycoproteins in differentiation and function.

Macrophages (mphi) play a crucial role in the immune system. The rat offers unique advantages for studying the biology of mphi. Firstly, monoclonal antibodies (mAb) against many rat mphi surface glycoproteins have become available. These have not only demonstrated a considerable heterogeneity among mphi, but have also allowed the characterization of various mphi surface molecules in terms of structure, expression regulation and function. Furthermore, substantial numbers of rat mphi can be isolated from various sites (e.g. blood, peritoneal cavity, lung and other tissues), enabling proper molecular and functional analysis of these mphi populations. Finally, a number of (unique) experimental models for human diseases have been developed in the rat, making possible the evaluation of the involvement of mphi in pathogenesis. For this, a method for the selective elimination of mphi from various tissues in vivo has proven very useful. Here, we will review the contribution that the rat has made to understanding the immunobiology of mphi. In particular, we will discuss the surface (glyco)proteins on rat mphi in differentiation and function, and the involvement of mphi in rat models of disease.

Animals↗
PubMed2001

Monoclonal antibodies against rat leukocyte surface antigens.

Monoclonal antibodies have proven to be powerful tools for studying the properties of leukocyte surface antigens and the cells that express them. In the past decades many monoclonal antibodies (mAb) for identifying the different rat leukocyte surface antigens have been described. A list of mAb is provided in Table I below. The rat leukocyte surface antigens are divided into different sections, including rat CD antigens (a), rat leukocyte surface antigens without CD designation (b), rat major histocompatibility complex (MHC) antigens (c), rat T-cell receptors (d) and rat immunoglobulins (e). The molecular and functional characteristics of rat leukocyte surface antigens are discussed in more detail in some of the other chapters of this issue (e.g. Van den Berg et al., p. 45). A more extensive overview of the properties of leukocyte surface antigens is provided by Barclay et al.

Animals↗
PubMed2001

IFN-beta1b augments glucocorticoid-induced suppression of tumor necrosis factor-alpha production by increasing the number of glucocorticoid receptors on a human monocytic cell line.

We studied the effect of recombinant interferon-beta1b (IFN-beta1b) on the sensitivity to glucocorticoids (GC) and on the number of GC receptors (GCR) in the human monocytic cell line THP-1. We found that IFN-beta1b augments the suppressive effect that dexamethasone has on the stimulated production of tumor necrosis factor-alpha (TNF-alpha), most likely related to the increased number of GCR observed after exposure to IFN-beta1b. This provides a possible clue to the mechanism of action of IFN-beta in multiple sclerosis.

Binding Sites↗
PubMed2000

Dexamethasone promotes phagocytosis and bacterial killing by human monocytes/macrophages in vitro.

One of the actions of glucocorticoids (GC) in multiple sclerosis (MS) is an inhibitory effect on demyelination. This can be caused by a reduction in the number of infiltrating macrophages and/or by an effect on the phagocytosis of myelin. Here we investigate the effect of GC on the phagocytosis of myelin. Contrary to what was expected, we found that incubation of human monocytes with dexamethasone (DEX) for 48 h augmented (approximately threefold) the phagocytosis of myelin. This enhancement of phagocytosis by human monocytes was not restricted to myelin. Phagocytosis of various particles mediated by different macrophage receptors was increased by DEX. We found that not only the phagocytosis of Staphylococcus aureus bacteria was augmented, but also the killing of these bacteria was at least twice as effective after culture with DEX. Tumor necrosis factor alpha production of human monocyte-derived macrophages induced by lipopolysaccharide and S. aureus was suppressed by DEX. Together our results show that DEX promotes the phagocytosis of particles by human monocytes and thereby may contribute to tissue repair after immune-mediated tissue damage or infection. These data shed a new light on the clinical application of GC.

Cells, Cultured↗
PubMed2000

Distinctive roles of neutrophils and monocytes in anti-thy-1 nephritis.

Anti-Thy-1.1 glomerulonephritis as an experimental model for mesangial proliferative glomerulonephritis was induced in Wistar rats by a single injection of monoclonal IgG2a-anti-Thy-1.1 antibody (ER4G). This transient model is complement-mediated and leads to mesangial-cell (MC) lysis followed by MC proliferation, glomerular microaneurysm formation, glomerular influx of polymorphonuclear leukocytes (PMNs) and macrophages, proteinuria, and hematuria. In this study we investigated the distinctive roles of infiltrating PMNs or monocytes/macrophages by treating rats with an antibody against rat integrin CD11b/CD18 (ED7) or by depletion of monocytes with multilamellar clodronate liposomes, respectively. ED7 administration resulted in reduction of the influx of PMNs in glomeruli during the first 6 days after induction of Thy-1.1 nephritis, whereas treatment with an isotype-matched irrelevant antibody (PEN9) or with phosphate-buffered saline had no effect on macrophage influx. Increased glomerular C3 and C6 deposition on days 1 and 3 was seen in the ED7-treated rats but not seen in the control groups. In addition, the ED7-treated group showed an increased number of aneurysmatic glomeruli and more severe hematuria. Monocyte/macrophage depletion led to a significant reduction of mesangial matrix expansion, although mesangial proliferation, proteinuria, and hematuria remained unaltered. These results, together with the known effects of PMN-derived enzymes on C3 cleavage, suggest that a reduction in the influx of PMNs results in sparing of C3 and consequently of more complement activation in the glomerulus with increased complement-mediated damage. Our data indicate that infiltrating PMNs and monocytes/macrophages play distinctive roles during inflammation in this model of MC glomerulonephritis.

Animals↗
PubMed2000

Ultrastructural localisation of sialoadhesin (siglec-1) on macrophages in rodent lymphoid tissues.

In previous studies it has been demonstrated that sialoadhesin is a macrophage-restricted adhesion receptor for lymphocytes and myeloid cells. It is under normal circumstances expressed by subpopulations of macrophages in lymphoid and haemopoietic tissues. In this study different immunoelectronmicroscopical techniques are used to investigate the ultrastructural localisation of sialoadhesin within the lymph node and spleen of rodents. The results show that sialoadhesin is selectively expressed by a subset of macrophages in peripheral lymphoid tissues. Sialoadhesin was localised predominantly on the plasma membrane and in particular in areas of intimate contact with lymphocytes, thereby visualizing putative local interaction between these cells. Interestingly, sialoadhesin was also detected in intracellular vesicles that were apparently taken up by macrophages. These findings are consistent with the putative role of sialoadhesin in local cell-cell interactions in lymphoid tissues. Surprisingly, sialoadhesin was also found at contact points of macrophages with other macrophages, sinus-lining cells and reticulum cells, suggesting that sialoadhesin also mediates interactions with these cell types.

Animals↗
PubMed2000

Kupffer cell depletion by CI2MDP-liposomes alters hepatic cytokine expression and delays liver regeneration after partial hepatectomy.

BACKGROUND: Although Kupffer cells (KCs) are capable of producing important growth-stimulating cytokines, their role in liver regeneration following partial hepatectomy (PH) remains poorly understood. METHODS: In the present study liver regeneration was studied after KC-depletion by intravenous administration of liposome-encapsulated dichloromethylene-diphosphonate (C12MDP), a method known to physically eliminate KCs. Furthermore, splenectomy was performed one week prior to PH to exclude the effect of C12MDP-liposomes on macrophage populations in the spleen. RESULTS: KC-depletion was confirmed in cryostat liver sections stained with the monoclonal antibody ED2, a marker for resident tissue macrophages. Forty-eight hours after PH, the cumulative hepatocyte DNA synthesis, as determined in liver sections by the hepatocyte bromodeoxyuridine labeling index, was significantly decreased in KC-depleted rats when compared to control-rats. The weight of the remnant liver, expressed as a percentage of the initial liver weight, was significantly less at 96 h after PH in KC-depleted rats. KC-depletion abolished the hepatic interleukin-6 (IL-6) and interleukin-10 (IL-10) mRNA synthesis and decreased hepatic expression of tumor necrosis factor-alpha (TNF-alpha), hepatocyte growth factor (HGF) and transforming growth factor-beta1(TGF-beta1) mRNA after PH, as was assessed by reverse-transcriptase polymerase chain reaction (RT-PCR). Moreover, at 4 h after PH the systemic release of IL-6 was significantly decreased in KC-depleted rats. CONCLUSION: We conclude that KCs are important for hepatocyte regeneration after PH. Delayed liver regeneration in KC-depleted rats can be explained, at least in part, by an imbalanced hepatic cytokine expression, thereby suppressing important growth-stimulating cytokines.

Animals↗
PubMed1999

The role of anti-myelin (auto)-antibodies in the phagocytosis of myelin by macrophages.

Plasma cells secreting antibodies directed to myelin components are present in CNS of MS patients and although the pathogenic role of such antibodies has yet to be established it is apparent from animal studies that anti-myelin antibodies are involved in myelin damage. In this study, we have investigated the effect of disease-promoting anti-myelin mAb on the phagocytosis of myelin by macrophages. Monoclonal antibodies directed to myelin basic protein (MBP)--clones 1, 12, 17, 22, 26, proteolipid protein (PLP), galactocerebroside (GalC) and myelin oligodendrocyte glycoprotein (MOG)--clones Y1, Y4, Y6, Y7, Y9, Y10, Y11 and Z12 were incubated with purified murine myelin labeled with DiI. The degree of phagocytosis of antibody-treated myelin by murine macrophages in vitro was determined using a quantitative flow cytometric assay. In comparison to untreated myelin pretreatment with myelin-specific mAb modified the degree of phagocytosis. The degree of opsonization of myelin was dependent on the isotype of antibody and the epitope recognized in addition to the ability of the mAb to fix complement. The greatest degree of opsonization of myelin was observed with the monoclonal antibody MOG Z12 that has previously been shown to enhance EAE and augment demyelination. These findings suggest a major role for anti-myelin antibodies, in particular antibodies directed to MOG, for the phagocytosis of myelin by macrophages in vitro. This may have relevance to the pathogenesis of myelin damage in vivo and provide a helpful tool for the classification of heterogeneous diseases such as MS.

Animals↗
PubMed1999

Regulation and functional involvement of macrophage scavenger receptor MARCO in clearance of bacteria in vivo.

The scavenger receptors expressed by macrophages are thought to play an important role in the immune response against bacteria by mediating binding and phagocytosis. A novel member of the class A scavenger receptor family, macrophage receptor with collagenous structure (MARCO), has recently been identified. In this study we have generated a panel of mAbs with specificities for different domains of this receptor. Two of those reacting with the C-terminal cysteine-rich domain block ligand binding of MARCO. The in vivo expression of this murine receptor is normally restricted to distinct populations of macrophages in the spleen and lymph nodes. During bacillus Calmette-Guérin (BCG) infection, during bacterial sepsis, or after the injection of purified LPS, however, the expression of MARCO is rapidly induced on macrophages in other tissues, including Kupffer cells in the liver. Using the mouse macrophage cell line J774.2, it was shown that LPS stimulation up-regulates surface expression of MARCO in a dose- and time-dependent fashion. The proinflammatory cytokines IL-1, IL-6, TNF-alpha, and IFN-gamma had little or no effect. Using inhibitory mAbs, the relevance of MARCO for the clearance of circulating bacteria in vivo was determined. Although the overall elimination of live Escherichia coli and Staphylococcus aureus from the blood did not appear to be affected by treatment with these Abs, the capturing of heat-killed bacteria by macrophages in the marginal zone areas of the spleen was clearly inhibited. This study suggests a role for MARCO in the host antibacterial defense.

Animals↗
PubMed1999

Regulation of CD 163 on human macrophages: cross-linking of CD163 induces signaling and activation.

CD163 is a member of the group B scavenger receptor cysteine-rich (SRCR) superfamily. This study describes aspects of the tissue distribution, the regulation of expression, and signal transduction after cross-linking of this receptor at the cell surface of macrophages. CD163 showed an exclusive expression on resident macrophages (e.g., red pulp macrophages, alveolar macrophages). The expression was inducible on monocyte-derived macrophages by glucocorticoids but not by interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon-gamma. The combination of IL-4 or GM-CSF with glucocorticoids resulted in a further increase. Subcellular analysis of alveolar macrophages by immunoelectron microscopy showed a plasma membrane localization of the antigen. Cross-linking of CD163 with monoclonal antibody induced a protein tyrosine kinase-dependent signal that resulted in (1) slow-type calcium mobilization, (2) inositol triphosphate production, and (3) secretion of IL-6 and GM-CSF. The data suggest a function for the SRCR-superfamily receptor CD163 in the regulation of inflammatory processes by macrophages.

Animals↗
PubMed1999

Differential effects of anti-rat CD11b monoclonal antibodies on granulocyte adhesiveness.

Four different monoclonal antibodies (mAbs) reactive with rat CD11b (ED7, ED8, OX-42 and 1B6c) have been characterized for their ability to induce homotypic aggregation of granulocytes or to modify granulocyte adhesiveness triggered by phorbol myristate acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP). Cross-blocking experiments showed that these mAbs recognize at least three different epitopes on CD11b. OX-42 mAb recognizes an inhibitory epitope since the mAb inhibited homotypic aggregation of granulocytes and their adherence to plastic in the presence of PMA or fMLP. ED7 and ED8 induced homotypic aggregation of granulocytes which was blocked by OX-42 and anti-CD18 mAb (WT3) suggesting that CR3 itself is involved in the adhesion process. The aggregation was dependent on active cell metabolism, intact cytoskeleton, divalent cations and activation of tyrosine kinases sensitive to genistein. Staurosporine, okadaic acid and orthovanadate potentiated the aggregation. ED7 and ED8 potentiated homotypic aggregation and adhesion of granulocytes to plastic caused by fMLP, but inhibited granulocyte adhesion to plastic induced by PMA. 1B6c recognizes an epitope that transmits a proaggregatory signal upon binding of the mAb but only if the granulocytes are in contact with plastic or are activated by fMLP. In contrast, 1B6c inhibited granulocyte adhesion to plastic triggered by PMA or fMLP. These data suggest the existence of functionally different epitopes on rat CD11b and indicate that some anti-CD11b mAbs are able to functionally activate CR3.

Animals↗
PubMed1998

Reactive oxygen species are required for the phagocytosis of myelin by macrophages.

Reactive oxygen species (ROS) are thought to be involved in the pathogenesis of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). In this study we showed that the phagocytosis of myelin by macrophages triggers the production of ROS. We also demonstrated that ROS play a crucial role in the myelin phagocytosis. Blocking the ROS production with NADPH oxidase inhibitors (100 microM DPI or 10 mM Apocynin) essentially prevented the phagocytosis of myelin. Furthermore, scavenging of ROS with catalase (H2O2) or mannitol (OH-) decreased the phagocytosis of myelin by macrophages, whereas superoxide dismutase (O2-) did not show this effect. In addition, Lipoic acid (LA), a non-specific scavenger of ROS, also decreased the phagocytosis of myelin by macrophages. In our results, we demonstrate for the first time that ROS appear to play a regulatory role in the phagocytosis of myelin.

Animals↗
PubMed1998

Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice.

Organ-specific autoimmune diseases are characterized by infiltrates, including T lymphocytes and activated macrophages. Macrophages and secondarily activated tissue resident counterparts can both present Ag to and contribute to cytokine secretion by T lymphocytes. We have previously shown a crucial role of peripheral macrophages in experimental allergic encephalomyelitis (EAE), a Th1-mediated demyelinating disease that serves as a an animal model for multiple sclerosis (MS), by their depletion using mannosylated liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP). Here we describe studies to investigate the mechanisms by which macrophages contribute to the lesion formation in EAE, by studying the effect of Cl2MDP-containing mannosylated liposomes (Cl2MDP-mnL) on adoptively transferred EAE in SJL/J mice. Adoptive transfer of EAE with myelin basic protein-reactive CD4+ T cells to SJL/J mice was abrogated by Cl2MDP-mnL treatment. CD4+ T cell and MHC II+ B220+ B cell extravasation from blood vessels and Th1 cytokine production were not inhibited. However, invasion of the central nervous system intraparenchymal tissues by lymphocytes, F4/80+, Mac-1+, and MOMA-1+ macrophages was almost completely blocked after treatment with Cl2MDP-mnL. Furthermore, in Cl2MDP-mnL-treated mice, the myelin sheaths appeared completely normal, whereas, in the control groups, marked demyelination occurred. Production of TNF-alpha and inducible nitric oxide synthase, both associated with macrophage/microglial activation, was inhibited. This intervention reveals a role for macrophages in regulating the invasion of autoreactive T cells and secondary glial recruitment that ordinarily lead to demyelinating pathology in EAE and multiple sclerosis.

Acute Disease↗
PubMed1998

Signal-regulatory protein is selectively expressed by myeloid and neuronal cells.

Signal-regulatory proteins (SIRP) are transmembrane glycoproteins with three extracellular Ig-like domains, closely related to Ag receptors Ig, TCR, and MHC, and a cytoplasmic domain with two immunoreceptor with tyrosine-based inhibition motifs that can interact with src homology 2 domain-containing phosphatases. SIRP have previously been shown to inhibit signaling through receptor tyrosine kinases, but their physiologic function is unknown. Here we demonstrate by expression cloning that the mAbs ED9, ED17, and MRC-OX41 recognize rat SIRP. In addition, we show for the first time that rat SIRP is selectively expressed by myeloid cells (macrophages, monocytes, granulocytes, dendritic cells) and neurons. Moreover, SIRP ligation induces nitric oxide production by macrophages. This implicates SIRP as a putative recognition/signaling receptor in both immune and nervous systems.

Amino Acid Sequence↗
PubMed1998

Discontinuation of treatment with IFN-beta leads to exacerbation of experimental autoimmune encephalomyelitis in Lewis rats. Rapid reversal of the antiproliferative activity of IFN-beta and excessive expansion of autoreactive T cells as disease promoting mechanisms.

IFN-beta has recently been shown to exert remarkable beneficial effects on disease development in patients with early stage relapsing-remitting MS. The specific immune mechanism(s) by which IFN-beta ameliorates this human demyelinating disease is at present undefined. One potential mechanism may reside in the antiproliferative activity of IFN-beta which may inhibit the expansion of autoaggressive T cells thereby limiting disease progression. In the present study we investigated whether the administration of recombinant rat IFN-beta (rrIFN-beta) to Lewis rats with actively induced experimental autoimmune encephalomyelitis (EAE) inhibits the expansion of encephalitogenic T cells in lymphoid organs and as such may contribute to suppression of disease activity in this widely used animal model for MS. Our data show that daily administrations of > or = 3 x 10(5) u rrIFN-beta to EAE rats, starting two days before MBP sensitization and continued for 10 days led to a dramatic and dose-dependent reduction in encephalitogenic T cells in both spleen and inguinal lymph nodes at day 8 post-immunization (p.i.). However, the rrIFN-beta-mediated reduction in effector T cells did not ameliorate paralytic disease as expected but significantly enhanced the severity of EAE. Analyses of lymphoid organs in the remission phase of EAE revealed strongly elevated numbers of encephalitogenic T cells in rrIFN-beta-treated versus control rats suggesting a rapid reversal of the antiproliferative action of rrIFN-beta followed by an overshoot in the subsequent expansion of these effector T cells. In conformity with higher numbers of encephalitogenic T cells and worsening of disease, animals also showed significantly greater perivascular inflammation in the CNS. The relevance of our findings in relation to the beneficial effects of IFN-beta in MS is discussed.

Adjuvants, Immunologic↗
PubMed1998

Effect of annexin-1 on experimental autoimmune encephalomyelitis (EAE) in the rat.

Annexin-1, a calcium-dependent phospholipid binding protein, has been shown to act as an endogenous central neuroprotectant, notably against cerebral ischaemic damage. In the present study we extend these findings to an animal model of multiple sclerosis, EAE, and report that endogenous annexin-1 is expressed in ED1+ macrophages and resident astrocytes localized within the lesions in the central nervous system (CNS). Intracerebroventricular (i.c.v.) administration of an NH2-terminal fragment spanning amino acids 1-188 of annexin-1 after the onset of the clinical symptoms significantly reduced both the neurological severity as well as weight loss of mild EAE. Immunoneutralization of endogenous brain annexin-1 failed to exacerbate the clinical features of EAE. Thus, although the role of endogenous annexin-1 in the pathogenesis of EAE remains to be determined, our findings suggest that annexin-1 may be of therapeutic benefit to the treatment of multiple sclerosis.

Animals↗
PubMed1998

Marrow-derived activated macrophages are required during the effector phase of experimental autoimmune uveoretinitis in rats.

PURPOSE: Experimental autoimmune uveoretinitis (EAU), an established model for human endogenous (autoimmune) posterior uveitis, is a CD4+ T cell-mediated disease inducible in Lewis rats by intradermal inoculation with retinal antigens. Immunohistochemical studies have previously documented the lymphocyte profiles during various stages of the disease process. The purpose of the present study was to investigate the role of macrophages in EAU. METHODS: EAU was induced in Lewis rats, and the effect of macrophage depletion, using the drug dichlorodimethylene diphosphonate (Cl2MDP) encapsulated in liposomes and administered intravenously, was assessed based on the clinical and histological profile of the disease. RESULTS: The results have shown that in control animals macrophages occur early, feature prominently throughout the course of the disease and display considerable heterogeneity: marrow-derived ED1+ cells and ED3+ cells are the major infiltrating cells, with many cells also expressing ED7 and ED8. In contrast, few cells expressed the ED2 antigen during EAU, even though ED2+ "resident" macrophages occur in the normal choroid. Macrophage depletion, using intravenously injected dichloromethylene diphosphonate (Cl2MDP) enclosed in liposomes, caused a delay in the onset and a reduction in the severity of EAU when administered during the "effector" stage of the disease, i.e. 9-11 days after inoculation with retinal antigen. The delay in disease onset was greater when liposomes were mannosylated and was accompanied by a reduction in the overall inflammatory cell infiltrate into the eye and reduced tissue damage. In addition, there was a reduction in the level of expression of MHC Class II antigen and CR3 (ED7) antigen, a marker of macrophage activation, in Cl2MDP-treated animals compared to controls. CONCLUSION: These results suggest that blood-borne, activated macrophages are major effectors of tissue damage during EAU.

Animals↗