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C D Dijkstra

Publications and source records attributed to C D Dijkstra.

At least 91 records · Page 5Linked to original sources
PubMed1993

Two different mechanisms of immune-complex trapping in the mouse spleen during immune responses.

The capacity of immune-complex (IC) trapping was examined using purified horse radish peroxidase (HRP)-anti-HRP (PAP) on frozen sections of mouse spleen in vitro. We investigated the trapping mechanisms by applying the IC with or without fresh mouse serum added on the spleen sections of naive as well as immunized mice. When the PAP was applied alone, it mainly located on the macrophages in red pulp. In the splenic white pulp of immunized mice, PAP was trapped on follicular dendritic cells (FDC) in a small area of the germinal center whereas it scarcely bound to the splenic white pulp of non-immunized mice. An antibody against mouse Fc receptor (2.4G2) blocked the trapping but antibodies against mouse complement receptor (8C12, Mac-1 and 7G6) did not. When the PAP was applied mixed with fresh mouse serum, it bound on FDC in the primary follicles in the spleen of non-immunized mice. The density and area of IC trapping increased in the spleen of immunized mice. IC trapping in the presence of fresh mouse serum was blocked by the antibodies 8C12 and 7G6 but not by 2.4G2 or Mac-1.

Animals↗
PubMed1993

Reversible depletion of synovial lining cells after intra-articular treatment with liposome-encapsulated dichloromethylene diphosphonate.

We studied the depletion and repopulation of synovial lining cells in mice. A single intra-articular injection of liposomes encapsulating the drug dichloromethylene diphosphonate (CL2MDP) in the mouse knee joint caused selective elimination of synovial lining cells. Depletion of cells occurred within a few days as evidenced by light microscopic, electronmicroscopic and immunohistochemical studies. Maximal depletion was seen on day 7. Repopulation was observed in the following weeks, starting at the bone side of the joint. Until day 30, full recovery (60% recovery) was not observed in the lining lying adjacent to the dermis. Side effects on cartilage metabolism, such as inhibition of proteoglycan synthesis or degradation of proteoglycans from the matrix was minor but significant, 1 and 2 days after liposome treatment but thereafter full recovery was observed. Selective elimination of lining cells from the joint enabled us to study the in vivo role of these cells in the onset and subsequent pathology of experimental arthritis. An immune-complex-mediated experimental arthritis elicited in lining cell depleted joints that had received CL2MDP-liposomes 7 days earlier prevented inflammation as compared to controls.

Animals↗
PubMed1993

Enhanced tumour growth in the rat liver after selective elimination of Kupffer cells.

The evidence that Kupffer cells are capable of controlling metastatic growth in the liver in vivo is largely circumstantial. The best approach when studying natural cytotoxicity activities of Kupffer cells is to investigate the effect of Kupffer cell elimination on tumour growth. Until now it has not been possible to eliminate Kupffer cells without affecting other cell populations. We have recently developed a new method to eliminate Kupffer cells selectively: intravenous injection of liposome-encapsulated (dichloromethylene)bisphosphonate (Cl2MDP-liposomes) leads to effective elimination of all Kupffer cells, without affecting non-phagocytic cells. Wag/Rij rats were injected with Cl2MDP-liposomes. After 48 h, rats were inoculated with syngeneic CC531 colon carcinoma cells by injection in the portal system. The results show a strongly enhanced tumour growth in the liver of the Cl2MDP-liposome-treated rats. In these animals, livers were almost completely replaced by tumour and had increased in weight, whereas in the control groups only a few (four to eight) small (1-mm) tumour nodules were found. These data show that selective elimination of Kupffer cells results in enhanced tumour growth in the liver, implying that Kupffer cells play a crucial role in controlling tumour growth in the liver.

Animals↗
PubMed1993

Selective elimination of macrophages by dichlormethylene diphosphonate-containing liposomes suppresses experimental autoimmune neuritis.

The injection of liposome-encapsulated dichlormethylene diphosphonate (Cl2MDP) constitutes an effective method to selectively eliminate phagocytic cells from spleen, liver and the circulation. We evaluated the effect of Cl2MDP-liposomes on the course of actively induced and adoptively transferred experimental autoimmune neuritis (EAN), both animal models of the human Guillain-Barré syndrome. Injection of Cl2MDP-liposomes 11 and 13 days postimmunization (p.i.) of Lewis rats with bovine peripheral nerve myelin efficiently prevented clinical signs of EAN up to day 15 p.i., when all control animals were affected. Thereafter, EAN gradually also developed in Cl2MDP-liposome-treated rats, but until day 19 disease was significantly milder than in control rats injected with buffer-filled liposomes. Adoptive transfer EAN (AT-EAN) induced by injection of activated P2-specific T cells could be suppressed even more markedly by application of Cl2MDP-liposomes 1, 3, and 6 days after cell transfer. Efficient suppression of AT-EAN by Cl2MDP-liposomes rules out the possibility that EAN is prevented due to interference with the induction phase of this experimental disease and confirms that macrophages are important effector cells during EAN. Selective suppression of phagocytic cell function by drug-containing liposomes may hold promise as a novel treatment of demyelinating autoimmune diseases of the nervous system.

Animals↗
PubMed1993

Demonstration of interleukin-1 beta in Lewis rat brain during experimental allergic encephalomyelitis by immunocytochemistry at the light and ultrastructural level.

Interleukin-1 beta (IL-1) is a cytokine which exerts many biological effects during inflammation. In the present study, experimental allergic encephalomyelitis (EAE) was induced in Lewis rats. During the various stages of EAE, the presence of IL-1 in the brain was investigated using immunocytochemistry at both the light and ultrastructural level. Ten days after immunization, IL-1 immunoreactivity was found in brains of animals which at this time showed mild clinical signs. Outside the blood-brain barrier, IL-1 was localized in the cytoplasm of meningeal macrophages and perivascular cells. Within the brain parenchyma, IL-1 immunoreactivity was distributed in perivascular lesions in the cytoplasm of infiltrated macrophages and activated microglia. On day 13, animals had developed a full blown EAE. At this stage the number of lesions with IL-1-positive cells had increased. In the remission phase (day 25), lesions with IL-1-positive cells could still be detected but were less pronounced as compared to day 13. Other presumptive IL-1-producing cell types like endothelial cells or astrocytes were, at none of the various stages, found to stain for IL-1.

Animals↗
PubMed1993

Multiple sclerosis: some possible therapeutic opportunities.

Multiple sclerosis (MS) is a human disease characterized by chronic demylination in the brain caused by immunological mechanisms involving T lymphocytes and macrophages. Recently developed models of chronic relapsing forms of experimental allergic encephalomyelitis, sharing many of the clinical and pathological features of MS, and new discoveries of efficient autoregulatory mechanisms intrinsic to the immune system, have suggested new possibilities for therapeutic intervention in MS. Moreover, recent data support the concept that the immune system is exposed to a broad framework of regulation, including neuroendocrine control. In particular, interfering with secretion of the lactogenic hormone prolactin and of glucocorticoids has consistently resulted in a reduction of clinical and pathological manifestations of the disease. In this review, Frank Berkenbosch and colleagues highlight several of the possible therapeutic opportunities for the treatment of MS.

Animals↗
PubMed1993

Macrophage populations in different stages of induced hepatic metastases in rats: an immunohistochemical analysis.

Macrophages play a role in the host defence against cancer. Little is known about changes in macrophage populations during early metastatic growth. To evaluate the distribution, number and phenotype of macrophages in the development of hepatic metastases in a rat model (Wag/Rij rats and syngeneic CC531 colon carcinoma cell line), an immunohistochemical study was performed with the monoclonal antibodies ED1 (monocytes, and all macrophages), ED2 (resident tissue macrophages, like Kupffer cells) and ED3 (a subpopulation of macrophages which may play a role in the recruitment of lymphocytes). OX19 and His14 were used to identify lymphocytes. In this study a new monoclonal antibody CC52 is described, which recognizes the CC531 tumour cell line. Liver metastases were induced by injection of CC531 colon carcinoma cells into a mesenteric vein. Rats were killed at various intervals. Results show three major macrophage populations during hepatic tumour growth: (1) on day 3, infiltrates are observed around the micrometastases, which contain mainly newly recruited macrophages (ED1+ and ED2-); (2) after 7 days, ED3-positive (ED3+) macrophages together with T lymphocytes are found in the infiltrates; (3) an increase in the number of ED2-positive (ED2+) Kupffer cells is observed in the liver parenchyma after 14 days. In conclusion, the present results suggest that various populations of macrophages, newly recruited (ED1+) as well as resident Kupffer cells (ED2+), are involved in the immune response against tumour cell deposits in the liver.

Adenocarcinoma↗
PubMed1993

Localization of beta 1 integrins and their extracellular ligands in human lymphoid tissues.

In this study, we describe the immunocytochemical distribution of the beta 1 integrins (alpha 1 to alpha 6) and their extracellular matrix ligands in human peripheral lymphoid tissues. The results show that within these tissues individual beta 1 integrins are differentially expressed by (sub)populations of stromal cells, including reticular cells, endothelial cells, epithelial cells, and sinus lining cells. The extracellular matrix components studied, eg, collagen I, III, and VI, fibronectin, laminin, and vitronectin, were predominantly associated with the stroma of the lymphoid tissues, and a unique distribution pattern was observed for each of them. Except for alpha 4 (and beta 1), low or no expression of the beta 1 integrins was found on lymphocytes, macrophages, interdigitating cells, and follicular dendritic cells. The results suggest that cell-matrix interactions play a major role in the maintenance of the complex spatial organization of the lymphoid tissue.

Child↗
PubMed1993

In vivo role of phagocytic synovial lining cells in onset of experimental arthritis.

The in vivo role of phagocytic synovial lining cells (SLC) was studied in acute experimental arthritis in the mouse. SLCs were selectively depleted by injecting liposomes encapsulating the drug dichloromethylene diphosphonate (CL2MDP, Clodronate). Optimal depletion of phagocytic lining cells occurred 7 days after CL2MDP liposome injection. Eliciting an immune complex-mediated arthritis in SLC-depleted knee joints largely prevented inflammation if compared to control arthritic knee joints. Joint swelling and influx of inflammatory cells into the joint cavity was markedly diminished. Cartilage damage, in this model related to influx of inflammatory cells, was significantly decreased. Reduced influx of inflammatory cells (mainly polymorphonuclear neutrophils) was correlated to a decreased production of chemotactic factors as measured in washouts of arthritic joints in a two-compartment Transwell system. Interleukin-1-driven chemotactic factors seem to be involved. Interleukin-1 levels were significantly lowered in SLC-depleted arthritic knee joints as compared to controls. Injection of recombinant murine interleukin-1 in SLC-depleted knee joints caused less influx of inflammatory cells as compared to injection into control knee joints. A specific damage of CL2MDP liposome treatment to synovial blood vessels was excluded as intraarticular injection of human recombinant C5a in lining-depleted knee joints showed similar influx of inflammatory cells if compared to human recombinant C5a injection in control knee joints. This study indicates that in immune complex-mediated arthritis, phagocytic lining cells regulate the onset of the inflammatory response.

Animals↗
PubMed1993

Two functionally different follicular dendritic cells in secondary lymphoid follicles of mouse spleen, as revealed by CR1/2 and FcR gamma II-mediated immune-complex trapping.

The capacity to trap immune complexes (IC) was examined using purified peroxidase-antiperoxidase IgG on frozen sections of mouse spleen. In the absence of serum, binding of IC was confined to macrophages in the red pulp. However, when IC were applied in the presence of fresh mouse serum as a source of complement, trapping occurred on follicular dendritic cells (FDC) in the primary follicles. Trapping was specifically inhibited with monoclonal antibodies against complement receptor type 1 (CR1) (8C12) and CR 1/2 (7G6), but not with anti-CR3 (Mac-1). The binding mechanism of IC in the secondary follicles of animals immunized with sheep red blood cells differed from that observed in unimmunized mice. Here, trapping occurred both in the absence and presence of fresh mouse serum. In the absence of fresh mouse serum, trapping on FDC was mediated by FcR gamma II, as demonstrated by blocking with monoclonal antibody 2.4G2. FcR gamma II-mediated trapping was only observed on a relatively small proportion of FDC that was located in the light zone of the secondary follicles, while complement receptor-mediated IC trapping was observed in more expanding areas, including dark zone and corona. These results show that both complement receptor as well as Fc receptor can function in the binding of IC to FDC. They also provide evidence for the existence of functionally different FDC populations in the secondary lymphoid follicles of mouse spleen.

Animals↗
PubMed1992

Sialoadhesin on macrophages: its identification as a lymphocyte adhesion molecule.

In this study we present evidence that the mouse and rat sialoadhesin (originally named sheep erythrocyte receptor) on macrophages can function as a lymphocyte adhesion molecule. Lymphocytes were shown to bind to the splenic marginal zone, and lymph node subcapsular sinus and medulla in a frozen section assay. Selective depletion experiments showed that binding was mediated by macrophages. Adhesion was blocked by preincubation of the sections with monoclonal antibodies against mouse or rat sialoadhesin. Binding was temperature dependent, divalent cation independent, and involved sialic acid residues on the lymphocyte, as it could be inhibited by prior neuraminidase treatment or addition of the ganglioside GD1a. Binding to sialoadhesin was confirmed using the purified receptor and was observed among T cells, T blasts, B cells, and B blasts. Isolated macrophages or dendritic cells showed little binding. Sialoadhesin provides the first example of a macrophage-restricted lymphocyte adhesion molecule.

Animals↗
PubMed1992

Selective inhibition of immune complex trapping by follicular dendritic cells with monoclonal antibodies against rat C3.

The role of complement component C3 in the trapping of immune complexes by follicular dendritic cells (FDC) was studied in the rat, by means of the C3-specific monoclonal antibody ED11. Immunocytochemistry revealed the presence of C3 on FDC, where it co-localized with trapped peroxidase anti-peroxidase complexes. Furthermore, C3 was detected on reticular cells occupying the T cell areas of peripheral lymphoid organs, which are not involved in the handling of immune complexes. The in vivo administration of anti-C3 abolished the trapping of immune complexes in splenic follicles, but was unable to release preexisting complexes from the FDC. Trapping of immune complexes was also prevented by treatment of rats with cobra venom factor (CoVF). While CoVF caused massive depletion of C3 from serum, ED11 treatment had no such effect. The effect of anti-C3 appeared at least in part to be due to an inhibition of complement activation by immune complexes. We also analyzed earlier stages of the trapping process, with respect to their C3 dependence. Upon systemic injection immune complexes are initially observed in the marginal zone. Administration of anti-C3 reduced this localization, indicating a role for C3 in the entry of immune complexes into the spleen. Our results confirm experiments in CoVF-treated animals and extend the evidence for a role of C3 in the follicular trapping process using anti-C3 in vivo. The mechanism of immune complex trapping and the role of complement therein is discussed.

Animals↗
PubMed1992

Determination of the origin and nature of brain macrophages and microglial cells in mouse central nervous system, using non-radioactive in situ hybridization and immunoperoxidase techniques.

The origin and nature of brain macrophages and microglial cells in the mouse central nervous system (CNS) were investigated. First, the expression and localization of determinants recognized by the different monoclonal antibodies (mAbs) MOMA-1, Mac-1-alpha, and F4/80 (raised against cells of the mononuclear phagocyte system) were immunohistochemically studied in the developing and adult mouse brain. In order to clarify the origin of brain macrophages and microglial cells, we used bacteriophage lambda transgenic mice as donors for bone marrow transplantations in recipient mice of different ages. During ontogeny, numerous MOMA-1-, Mac-1-alpha-, and F4/80-positive blood monocyte-derived brain macrophages (amoeboid microglia) infiltrated the CNS parenchyma. These brain macrophages gradually disappeared from the brain parenchyma at postnatal day 7 (P7). From P17 on, Mac-1-alpha- and F4/80-positive cells were detected within the brain parenchyma with the morphology of resting microglial cells. Transitional forms between brain macrophages and "resting" microglia were not observed in the developing brain. Combined non-radioactive in situ hybridization and immunohistochemistry revealed many MOMA-1-positive bone marrow-derived brain macrophages that were located in the leptomeninges, the ventricles, and occasionally the blood vessel walls. These results show that brain macrophages are of bone marrow origin. Many "resting" microglial cells were detected in the brain, mainly in the white matter. It appeared that about 10% of these cells displayed the transgenic signal. This result indicates that the majority of "resting" microglial cells are of local, presumably neuroectodermal, origin.

Animals↗
PubMed1992

Detection of migrated allogeneic oligodendrocytes throughout the central nervous system of the galactocerebrosidase-deficient twitcher mouse.

Galactocerebrosidase-deficient oligodendrocytes of 'twitcher' (twi/twi) mice degenerate prematurely. Transplantation of normal bone marrow cells has been shown to alleviate symptoms and to prolong survival time. However, characteristic ataxia ('twitching') is not cured. In an attempt to improve further the condition of twitcher mice, allogeneic foetal liver cells were transplanted as a source of normal haemopoietic stem cells and supplemented with intracerebral transplantation of foetal brain cells. A reliable method was developed to detect donor-type cells in brain tissue. Bacteriophage lambda transgenic foetal mice were used as donors of both foetal liver and brain cells. Integrated copies of lambda DNA in donor cells were detected by in situ hybridization with biotinylated probes, which were then stained using streptavidin alkaline phosphatase. This technique was combined with immunohistochemistry to distinguish donor-type oligodendrocytes from macrophages. Immunoperoxidase staining with an antiserum to carbonic anhydrase-II produced dark perikarya of oligodendrocytes. The results demonstrated that local foetal brain cell grafts resulted in a wide dissemination of donor-type oligodendrocytes throughout the twitcher brain. The addition of a foetal brain cell graft to haemopoietic cell transplantation resulted in significantly prolonged survival of twitcher mice.

Animals↗
PubMed1992

The role of macrophages in demyelination.

Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS). In particular in the CsA-induced chronic relapsing form (CREAE), pronounced demyelination occurs, in temporal association with relapses. It is still a matter of discussion which cell type ultimately is responsible for the actual process of demyelination. Macrophages, cytotoxic T lymphocytes and also astrocytes are possible candidates. In this short overview, the role of macrophages in the pathogenesis of EAE is discussed. It is shown that in particular, newly recruited macrophages play a crucial role in the generation of clinical signs. Possible mechanisms by which macrophages are involved in the pathogenesis of demyelinating diseases are presented.

Animals↗
PubMed1992

Liposome mediated affection of monocytes.

Dichloromethylene diphosphonate (Cl2MDP) enclosed in liposomes, when injected intravenously, selectively eliminates all phagocytizing macrophages that are in direct contact with the blood circulation of the spleen and the liver. We examined whether Cl2MDP containing liposomes affect, in addition, rat monocytes and bone marrow macrophage precursors (BMMP's). In addition to Phosphatidylcholine-Cholesterol liposomes (PC liposomes), we also used mannosylated PC liposomes (PCMAN liposomes), which are reported to bind more efficiently to macrophages. Monocytes appeared to be affected 24 h after injections of 2 ml of Cl2MDP containing PC as well as PCMAN liposomes. In addition, almost no macrophages could be detected in one week cultures of blood leukocytes isolated from these animals; cultures from control animals contained +/- 50% macrophages. Bone marrow macrophage precursors did not appear to be affected.

Animals↗