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C D Dijkstra

Publications and source records attributed to C D Dijkstra.

At least 73 records · Page 4Linked to original sources
PubMed1995

Postmortem delay effects on neuroglial cells and brain macrophages from Lewis rats with acute experimental allergic encephalomyelitis: an immunohistochemical and cytochemical study.

The effects of increasing postmortem delay (PMD) times on morphological, immunological and functional characteristics of various brain cells both in situ and in vitro were studied in postmortem brain tissue derived from rats with acute experimental allergic encephalomyelitis (EAE). A decline of the brain tissue structure was first noted after a PMD of 6 h. Radial glia in the cerebellum were frequently interrupted and retractions artifacts appeared around brain cells. However, even after the longest PMD interval of 18 h the quality of the cell and tissue structure was still good enough for immunohistochemical characterization. Immunohistochemical staining of frozen and fixed rat brain tissue sections resulted in an enhancement of the immunoreactivity after a PMD of 4 h, using a panel of mono and polyclonal antibodies directed against glial fibrillary acidic protein (GFAP), basement membranes (laminin), brain macrophage antigens (ED1 and ED2), and various immunologically important surface molecules, such as major histocompatibility complex (MHC) class II (Ia) antigen (OX6), CR3 complement receptor (ED8), and leukocyte common antigen (OX1). No increase in staining intensities with the ED1, ED8 and OX6 mAbs specific for macrophage antigens could be detected on brain macrophages that were isolated from brain tissue of rats with EAE obtained after various PMD intervals. Irrespective of the PMD interval, viable astrocyte cell cultures were obtained with comparable staining intensities for GFAP. These cultured astrocytes were capable of ingesting Latex beads and were highly proliferative as measured by BrdU uptake, at all investigated PMDs. Thus, even after long PMD intervals, brain material can be used successfully. Other data suggest that the situation is similar to human brain material, even though the PMD times may be somewhat different.

Acute Disease↗
PubMed1995

Macrophages in T cell line-mediated, demyelinating, and chronic relapsing experimental autoimmune encephalomyelitis in Lewis rats.

About 50% of the mononuclear cells in the perivascular lesions in the central nervous system (CNS) of rats suffering from experimental allergic encephalomyelitis (EAE) are blood-borne macrophages. In this study we investigated the role of these macrophages in different variants of EAE, using a liposome-mediated macrophage depletion technique. Intravenously injected liposomes containing dichloromethylene diphosphonate (Cl2MDP) are ingested by macrophages and cause temporary and selective elimination of these cells. Macrophage depletion during EAE induced by a T cell line specific for myelin basic protein (MBP; T cell-EAE) suppresses development of neurological signs of EAE. T cell-EAE with pronounced demyelination as induced by an additionally injected MoAb directed against myelin oligodendrocyte glycoprotein (MOG) was also significantly ameliorated after macrophage depletion. During chronic relapsing EAE (CR-EAE) the occurrence of relapses was prevented or suppressed, provided that the liposomes were injected before the initiation of a putative relapse. A chronic progressive course of CR-EAE was not modified by Cl2MDP containing liposome treatment. Histologic examination of the CNS of liposome-treated animals confirmed decreased infiltration of macrophages into the parenchyma in the rats with T cell and AD-EAE, whereas T cells were still present.

Animals↗
PubMed1995

Anti-CD11b/CD18 antibodies reduce inflammation in acute colitis in rats.

The influx of monocytes and neutrophils into the inflamed tissue could be an important aspect in the pathogenesis of inflammatory bowel disease (IBD). A membrane protein involved in the monocyte/neutrophil adherence to endothelium is CD11b/CD18 or alpha M beta 2 (complement receptor type 3 = CR3). In the present study the role of CD11b/CD18 in experimental IBD was studied by treatment with ED7 and OX42, two MoAbs against CD11b/CD18. Colitis was induced in rats by a single, rectal administration of 30 mg 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol 30%. Two hours before and 3 days after induction of colitis, the animals were given an i.v. dose of 0.5 mg of either ED7 or OX42 in 1 ml PBS. Controls received PBS or an irrelevant MoAb. Four days after the last treatment with the antibodies, the rats were killed, and macroscopic damage scores of the colon were determined. Macrophages and granulocytes were studied by immunohistochemistry and quantified by Interaktives Bild Analysen System (IBAS), and myeloperoxidase (MPO) activity in colonic tissue was measured. After treatment with ED7 and OX42 the mean damage score of the colon was reduced from 4.2 in IBD animals to 1.0 and 1.3, respectively. Smaller areas of ulcerations and a decrease in the number of ulcerations were observed compared with PBS-treated rats. Furthermore, the amount of infiltrating monocytes and leucocytes in the submucosa was enormously reduced, as well as MPO activity in the colonic tissue. These results show that treatment with MoAbs against CD11b/CD18 reduces clinical signs of experimental IBD in rats by a partial blockade of infiltrating macrophages and granulocytes.

Acute Disease↗
PubMed1995

A novel rat mesangial matrix protein, MMP-50/100, involved in mesangial glomerulopathies.

BACKGROUND: Within the glomerular extracellular matrix, the glomerular basement membrane and the mesangial matrix have different compositions, presumably related to their different functions. In this study, a novel mesangial matrix protein is recognized by mAb ED5 and KiM4R, which were originally selected for reactivity with follicular dendritic cells of rat lymphoid organs. EXPERIMENTAL DESIGN: Distribution of this mesangial matrix protein (MMP-50/100) was studied in normal Wistar rat kidneys by indirect immunofluorescence and immunoelectron microscopy. For partial immunobiochemical characterization, ED5-affinity-purified glomerular matrices were subjected to SDS-PAGE analysis. Expression of MMP-50/100 was additionally studied in kidneys of rats depleted for complement and in kidneys of rats depleted for resident macrophages. Functional significance of MMP-50/100 was studied in kidneys of rats with mesangial glomerulopathies. RESULTS: Immunoelectron microscopy showed that MMP-50/100 is located in the extracellular matrix of the rat renal mesangium between mesangial cells and the basement membrane and on the mesangial cell membrane. SDS-PAGE analysis of affinity-purified glomerular matrices indicated that MMP-50/100 is a polypeptide glycoprotein with chains of apparent molecular weights of 50 and 100 kDa. Both in vivo and in vitro results indicate that MMP-50/100 does not appear to be a complement factor, or an Fc or complement receptor. In rats partially depleted for resident macrophages, the expression of MMP-50/100 was similar to that in control rats. In rats with BSA-induced chronic serum sickness nephritis, in rats with anti-Thy-1 nephritis, and in rats with uninephrectomy-induced focal glomerular sclerosis, the mesangial expression of MMP-50/100 was significantly increased. In the first model, double-label immunofluorescence demonstrated identical localization of MMP-50/100 with mesangial immune complex deposits. CONCLUSIONS: We conclude that MMP-50/100 is an intrinsic component of the mesangial matrix, presumably related to the "classic" mesangial cell. Expression of MMP-50/100 is increased in expanded mesangial matrices during development of glomerular disease. Furthermore, MMP-50/100 appears to be involved in the handling of mesangial immune complexes.

Animals↗
PubMed1995

Host origin of follicular dendritic cells induced in the spleen of SCID mice after transfer of allogeneic lymphocytes.

Follicular dendritic cells (FDC) are uniquely characterized by the ability to trap immune complexes. In a previous report, it was shown that functional FDC with the capacity to trap immune complexes via complement receptor emerged in the splenic follicle after transferring syngeneic lymphocytes into the severe combined immunodeficiency (SCID) mouse. In the present report, we have investigated whether FDC are derived from haematopoietic cells or surrounding stromal components, by transferring allogeneic lymphocytes into SCID mice. Transfer of allogeneic T and B lymphocytes (H-2k) into SCID(H-2d) mice, however, failed to induce the development of FDC in the splenic white pulp. This was due to a graft-versus-host reaction (GVHR) by allogeneic lymphocytes against host stromal cells, as revealed by the destruction of the splenic reticular meshwork. The GVHR was prevented in transfer experiments of T-cell-depleted allogeneic lymphocytes with daily administration of anti-Thy-1 antibody. This resulted in segregated lodgement of allogeneic B lymphocytes in the proper compartments and, thereafter, generation of FDC in the primary follicle of SCID spleen, as revealed by the trapped immune complexes via complement receptors. The H-2 of the newly generated FDC was examined by two-colour immunofluorescent staining. FDC were defined as the reticular cells stained with anti-CR1/2 or FDC-M1 antibodies. FDC carried host H-2, clearly indicating that newly generated FDC are host-derived. In addition, the FDC shared the BP-3 protein with the surrounding reticular cells, a specific marker of reticular meshwork in the murine lymphoid tissues, and formed a network continuous with the rest of the reticulum, suggesting that FDC and non-FDC reticular cells belong to the same cell lineage.

Animals↗
PubMed1994

Phagocytic activity of macrophages and microglial cells during the course of acute and chronic relapsing experimental autoimmune encephalomyelitis.

The ED1 monoclonal antibody recognizes an antigen in lysosomal membranes of phagocytes. The expression of this antigen in cells increases during phagocytic activity. Here we describe the expression of ED1-immunoreactivity during the various stages of both acute (monophasic) and chronic relapsing experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. During the first attack of acute and chronic relapsing EAE, ED1-immunoreactivity was present in macrophages and in cells which displayed morphologic features of activated microglial cells (i.e., cells with thick short processes). At the ultrastructural level these cells were seen to contain phagocytosed myelin structures in lysosomes. ED1-immunoreactivity in these cells was present in the cytoplasm near lysosomes. During the remission phase of acute EAE and the relapse phase of chronic relapsing EAE, ED1-positive cells with dendritic morphology not only were present in or nearby lesions, but were also found at sites distant from lesions throughout large parts of the brain. These cells had a morphology comparable to microglial cells in normal brain. A major difference between animals which were in remission and animals which on day 25 were suffering from a relapse, was that the latter showed the presence of lesions with darkly stained round ED1-positive macrophages and activated microglial cells. These results indicate that during a relapse, newly recruited blood-borne macrophages infiltrate the brain and, together with activated lymphocytes and microglial cells, recommence a new demyelination process.

Acute Disease↗
PubMed1994

The functional state of follicular dendritic cells in severe combined immunodeficient (SCID) mice: role of the lymphocytes.

In the present study, we have investigated the capacity of follicular dendritic cells (FDC) to trap immune complexes (IC) in the splenic white pulp of severe combined immunodeficient (SCID) mice and the influence of lymphocyte transfer on FDC function. FDC are absent in the splenic white pulp of naive SCID mice as revealed by in vitro IC trapping assay. One week after transfer of syngeneic lymphocytes, functional FDC with complement receptors appeared in the primary follicles coincident with B cell segregation, and IC were trapped on those FDC in a complement-dependent manner. Next, we immunized the reconstituted SCID mouse to see whether another type of FDC could be induced in the secondary follicle. Antigenic stimulation induced FDC with an additional capacity to capture IC via FcR gamma II. As seen in immunocompetent mice, this type of FDC was located only in the light zone of the secondary follicle. The newly generated FDC did not carry H-2 antigen of transferred lymphocytes from F1 mice. In SCID mice, in which normally no functional FDC are detectable, the microenvironments of the splenic white pulp have a capacity to develop and differentiate normally after transfer of lymphocytes. Apparently, the generation of functional IC-trapping FDC causes the induction of complement receptor(s) and Fc receptor on meshwork cells, which requires the presence of the lymphocytes.

Animals↗
PubMed1994

Role of beta 2 integrins in the recruitment of phagocytic cells in joint inflammation in the rat.

Adhesion molecules of the beta 2 family of integrins play an important role in adhesion and migration of leukocytes to inflammatory sites. Several in vivo studies indicate that not only monoclonal antibodies (mAbs) directed against the common beta subunit (CD18) but also to the individual alpha subunits (CD11a, CD11b) can effectively inhibit different types of inflammation. In this study we report that in the adjuvant arthritis (AA) alpha CD11a, alpha CD11b, or even alpha CD18 treatment could not prevent disease development. Moreover, we examined the same mAbs in an acute nonspecific inflammation at different sites in the rat. We found that pretreatment with alpha CD11a or alpha CD11b could significantly block a zymosan peritonitis, but appeared to have no effect on a locally induced joint or dermal inflammation. Interestingly, alpha CD18 treatment, which blocks the entire CD11/CD18 complex, was able to inhibit the influx of inflammatory cells in a peritonitis as well as in a joint and dermal inflammation. These data not only indicate that the type of joint inflammation determines which adhesion molecules play a role in transendothelial migration, but also that involvement of the beta 2 integrins is highly site specific.

Animals↗
PubMed1994

Therapeutic effect of the D2-dopamine agonist bromocriptine on acute and relapsing experimental allergic encephalomyelitis.

We examined the effect of bromocriptine (BCR) treatment on the duration and severity of neurological symptoms of acute experimental allergic encephalomyelitis (EAE), an animal model for demyelinating diseases, particularly multiple sclerosis. To mimic the clinical situation, BCR treatment was started after the onset of clinical signs. Furthermore, the effect of BCR treatment on the course of a chronic relapsing form of EAE was studied. BCR was injected at daily intervals in a dose that resulted in sustained suppression of plasma concentrations of prolactin, a pituitary hormone that plays a role in immunoregulation. In acute EAE, BCR therapy reduced both severity and duration of the clinical signs. In chronic relapsing EAE, BCR treatment did not affect the severity and duration of the first attack, but reduced the duration of the subsequent, second attack. Thus, BCR treatment improves the clinical course in animals with ongoing disease. These findings may have implications for the search for new therapeutic approaches in multiple sclerosis.

Adrenocorticotropic Hormone↗
PubMed1994

Effect of K+ channel blockers on the clinical course and histological features of experimental allergic encephalomyelitis.

INTRODUCTION: Beneficial clinical effects of 4-aminopyridine (4-AP) in multiple sclerosis (MS) have been reported. The use of 4-AP in MS is based upon its ability to facilitate conduction in axons blocked by demyelination. This improvement is due to blocking of potassium (K+) channels in these fibres. Because K+ channels also play an important role in immune mechanisms successful treatment with K+ channel blockers in neuroimmunological diseases may have several causes. Therefore it seems important to study effects of K+ channel blockers in animal models of autoimmune disease. MATERIAL & METHODS: We studied the effects of 4-AP and quinidine on actively induced acute experimental allergic encephalomyelitis (EAE) in Lewis rats. RESULTS: There was no effect on the incidence of the disease. The severity of the disease was also unchanged although the disease duration was slightly diminished in the treated groups. Immunohistological comparison between the animals of different groups showed no differences. CONCLUSION: We conclude that 4-AP and quinidine are not capable of significantly changing the clinical course of EAE.

4-Aminopyridine↗
PubMed1994

Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1.

The monoclonal antibody (mAb) ED1 is being used widely as a marker for rat macrophages. The distribution of the recognized antigen in tissues and isolated cells strongly supports this use as a macrophage marker, since the majority of macrophages are recognized and only seldomly are other cell types stained by mAb ED1. In the present study we further characterized the recognized antigen by a detailed description of the localization of the antigen and by determining biochemical and functional properties. We show that the antigen is expressed on the membranes of cytoplasmic granules, like phagolysosomes, as well as on the cell surface. The amount of ED1 expression in a single cell can be correlated to phagocytic activity of the respective cell type, but the mAb ED1 is not able to block latex phagocytosis or bacterial killing. The mAb ED1 appears to recognize a heavily glycosylated protein of 90,000-110,000 MW, depending on the cell type used as antigen source. A possible relation with other known lysosomal glycoproteins with a similar molecular weight is discussed.

Animals↗
PubMed1994

Role of phagocytic macrophages in induction of contact hypersensitivity and tolerance by hapten applied to normal and ultraviolet B-irradiated skin.

Liposomes containing the drug dichloromethylene diphosphonate (Cl2MDP) can eliminate phagocytic cells, such as macrophages, when injected in vivo. In this paper we report that Cl2MDP-containing liposomes have been used experimentally to determine the extent to which cutaneous macrophages participate (1) in the induction of contact hypersensitivity (CH) when hapten is painted on normal murine skin, and (2) in the induction of CH or tolerance when hapten is painted on murine skin that has been exposed to ultraviolet B (UVB) radiation. Intradermal (i.d.) injections of Cl2MDP-containing liposomes were found to have no deleterious effects on CH induction via normal skin, whether the amount of hapten (dinitrofluorobenzene) applied to the cutaneous surface was optimal or excessive. Moreover, Cl2MDP-containing liposomes did not deplete the epidermis of Langerhans' cells. However, similar i.d. injections of Cl2MDP-containing liposomes did prevent the induction of CH when hapten was painted on UVB-irradiated skin of BALB/c mice, a strain that develops CH when hapten is applied to UVB-exposed skin. These findings indicate that the antigen-presenting cell (APC) function found in skin of UVB-resistant mice following exposure to UVB radiation can be attributed to macrophages. This explains why these mice develop and display CH after UVB radiation. By contrast, i.d. injections of Cl2MDP-containing liposomes failed to prevent the induction of the tolerance when hapten was applied to the surface of UVB-exposed skin of UVB-susceptible mice, such as C57BL/6. Since the dermis of UVB-exposed skin of these mice is known to contain a novel population of cells that can provide a tolerance-conferring signal, the current findings rule out macrophages as the responsible cell type.

Animals↗
PubMed1994

Prevention of corneal allograft rejection in rats treated with subconjunctival injections of liposomes containing dichloromethylene diphosphonate.

PURPOSE: The drug dichloromethylene diphosphonate (CL2MDP) encapsulated in liposomes depletes macrophages but not other immunocompetent cells. The authors investigated whether subconjunctival injection of CL2MDP containing liposomes (CL2MDP-LIP) could prolong survival of corneal allografts in rats. METHODS: Male Fisher rats received orthotopic corneal grafts of Dark Agouti origin. Rats were treated postoperatively with subconjunctival injections of 0.1 ml CL2MDP-LIP at the time of transplantation and on days 2, 4, 6, and 8 after transplantation. Control groups received either liposomes containing phosphate-buffered saline subconjunctivally at the same time points or no additional treatment. Corneal grafts were evaluated every other day and were scored for neovascularization, opacity, and edema. Immunohistologic evaluation was performed 12 and 19 days after surgery. RESULTS: Corneal grafts in both control groups were rejected within 17 days. In the Cl2MDP-LIP treated rats, grafts were not rejected during the maximum follow-up of 100 days. Cellular infiltration in these grafts was clearly reduced. There was also a strong reduction in neovascularization of the cornea. CONCLUSIONS: Rejection of orthotopic allogeneic corneal grafts could be prevented by repeated subconjunctival injection of Cl2MDP-LIP.

Animals↗
PubMed1993

Isolation of cytotoxic Kupffer cells by a modified enzymatic assay: a methodological study.

Kupffer cell (KC)-mediated cytotoxicity against tumor cells is of interest, since the liver is a major site of metastatic growth of primary colorectal cancer. KC isolation methods from rat livers, to study the tumoricidal properties of these cells, are based on perfusion of the liver and are therefore not suitable for human KC isolation from liver biopsies. In view of application to isolate KC from small wedge human liver biopsies, we have developed an isolation procedure for rat KC that does not require perfusion techniques. Liver tissue fragments were incubated with pronase with continuous pH registration and neutralization. KC were subsequently separated from other non-parenchymal cells by Nycodenz gradient centrifugation and purified by counterflow centrifugal elutriation. KC and other non-parenchymal cells were identified by immunophenotyping with a cytoplasmic monoclonal antibody ED1 and by ultrastructural analysis. About 3 x 10(6) KC per gram liver were isolated with a final purity of > 95% without loss of viability. To ensure that functionally competent KC were isolated, we assayed cytotoxicity against CC531 tumor cells in a recent developed cell-mediated MTT assay. Maximum cytotoxicity of KC was approximately 40% at an effector to target ratio of 10. In conclusion our approach seems to be a useful and simple method to isolate KC with good functional properties from rat livers, without the need for perfusion techniques.

Animals↗
PubMed1993

Treatment with anti-CR3 antibodies ED7 and ED8 suppresses experimental allergic encephalomyelitis in Lewis rats.

Experimental allergic encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS). Among the leukocytes which infiltrate the CNS during EAE, numerous macrophages are present. These macrophages are thought to play a crucial role in the generation of tissue damage and attendant neurological deficits. The mechanism by which the macrophages migrate across the blood-brain barrier is not yet clear. Membrane proteins involved in macrophage adherence to the endothelium include the CD11b/CD18 integrin, also known as the type 3 complement receptor (CR3). In this study we show that two monoclonal antibodies (mAb) ED7 and ED8 are directed against rat CR3. In addition, these mAb reduce recruitment of myelomonocytic cells towards thioglycollate induced peritonitis by 15-33%. This indicates that both ED7 and ED8 interfere with an epitope on CR3, which is involved in recruitment of phagocytes towards inflammatory lesions. Intravenous injection of ED7 and ED8 suppressed clinical signs of EAE. MRC OX-42, which also recognizes CR3, did not reduce thioglycollate-induced phagocyte recruitment into the peritoneum, and had no effect on EAE. These findings suggest that CR3 plays a role in the recruitment of macrophages towards the inflamed CNS of EAE animals, and confirm the role of macrophages in the generation of clinical signs of EAE. Involvement of CR3 in other phagocyte immune functions during EAE is discussed.

Animals↗
PubMed1993

The significance of in-situ Ia antigen expression in the pathogenesis of autoimmune central nervous system disease.

Major histocompatibility class II antigen (Ia) expression is thought to play an important role in the pathogenesis of autoimmune central nervous system (CNS) disease. It has been suggested that Ia expression within the CNS might be sufficient to induce experimental allergic encephalomyelitis (EAE). The expression of Ia antigen in the CNS was studied during the natural course of both acute and chronic relapsing EAE. We found that Ia expression in the CNS starts at a relatively late stage in the course of EAE and persists after the disappearance of the clinical signs. In order to further evaluate the functional significance of Ia expression on glial cells we also studied the effect of intraventricular administration of interferon-gamma. This caused widespread Ia expression within the CNS but no signs of autoimmune CNS disease. Based on these results and data from the literature, the role of local Ia expression in the CNS is reconsidered. In certain circumstances Ia expression may contribute to suppressive rather than enhancing effects on the immune response.

Acute Disease↗