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Biomedical subjects

G Kraal

Publications and source records attributed to G Kraal.

At least 55 records · Page 3Linked to original sources
PubMed1995

Cloning of a novel bacteria-binding receptor structurally related to scavenger receptors and expressed in a subset of macrophages.

A novel murine plasma membrane protein has been identified in subpopulations of macrophages. It has an intracellular N-terminal domain, a transmembrane domain, and an extracellular region with a short spacer, an 89 Gly-Xaa-Yaa repeat-containing collagenous domain, and a C-terminal cysteine-rich domain. In situ hybridization and immunohistochemical staining have localized the protein to a subset of macrophages in the marginal zone of the spleen and the medullary cord of lymph nodes. No expression was observed in macrophages of liver or lung. Transfected COS cells synthesized a native trimeric plasma membrane protein that bound labeled bacteria and acetylated LDL, but not yeast or Ficoll. The results suggest that the novel protein is a macrophage-specific membrane receptor with a role in host defense, as it shows postnatal expression in macrophages, which are considered responsible for the binding of bacterial antigens and phagocytosis.

Amino Acid Sequence↗
PubMed1995

Increased specific IgE production in lungs after the induction of acute stress in rats.

Under normal conditions, immune responses in the lung are suppressed, resulting in low antigen-specific serum antibody titers after intratracheal immunization of rodents. We attempted to determine whether mild inescapable electric foot-shock stress, immediately followed by intratracheal instillation of trinitrophenyl-conjugated keyhole limpet hemocyanin, could enhance the primary and secondary humoral immune responses in male Wistar rats. This acute emotional stress paradigm and subsequent intratracheal administration of trinitrophenyl-conjugated keyhole limpet hemocyanin resulted in a dramatic increment of trinitrophenyl-specific immunoglobulin isotype concentrations in serum, including IgE. Analysis of paratracheal lymph node and spleen tissue for trinitrophenyl-specific antibody-forming cells revealed that the increased specific antibody concentrations resulted from a local production in the paratracheal lymph nodes. Because the presence of aeroantigen-specific IgE is associated with diseases such as allergic asthma, we advocate the view that acute emotional stress can contribute to the onset or severity of allergic asthma by lowering the threshold of induction of aeroantigen-specific IgE production in the lungs.

Animals↗
PubMed1995

Oral tolerance is determined at the level of draining lymph nodes.

In the skin and in the epithelium of the oral mucosa a comparable network of Langerhans cells can be found. Antigen application on either epithelium leads to rapid emigration of Langerhans cells to the draining lymph nodes. Application on the oral mucosa leads to tolerance induction while application on the skin results in sensitization of the animal. Here we show that there are no differences in the antigen presentation capacity of oral mucosa- and skin-derived dendritic cells. However, measurement of IFN-gamma and IL-5 production, as representatives of Th1 and Th2 cytokines respectively, in total lymph node suspensions after sensitization via the skin or oral mucosa demonstrated a skewing of the response towards Th2 after antigen application on the oral mucosa. Together with our previous studies, in which it was shown that oral tolerance induction is not inherent to oral mucosa-derived dendritic cells, we postulate that oral tolerance is determined at the level of draining lymph nodes influenced by local cytokine profiles.

Administration, Cutaneous↗
PubMed1995

Homing of lymphocytes into islets of Langerhans in prediabetic non-obese diabetic mice is not restricted to autoreactive T cells.

Non-obese diabetic mice spontaneously develop a type 1 diabetes. The entry of leukocytes in the islets of Langerhans was studied in untreated and in irradiated mice. FITC-labeled cells from spleen, lymph nodes or bone marrow of healthy or diabetic donors did home to the inflamed islets of unmanipulated recipients. B and T cells migrated equally well, whereas rare neutrophils entered the islets. Lymphocyte homing was blocked by anti-L-selectin and anti-alpha 4 integrin antibodies. Insulitis transfer experiments using mice congenic at the Thy-1 locus showed that anti-alpha 4 integrin treatment totally inhibited the migration of donor type T cells in the islets, whereas anti-L-selectin only had an early and transient effect. The expression of vascular addressins in the islets was linked to the presence of mononuclear cells. Thus, in the developing islet infiltrate, the entry of cells appears continuous and restricted to lymphocytes, whether autoreactive or not, and involves the L-selectin. This mechanism rather promotes the migration of naive-type cells. Conversely, during the adoptive transfer of insulitis the entry of L-selectin- diabetogenic T cells is highly favored, to the detriment of L-selectin+ naive type cells.

Animals↗
PubMed1995

Changes in cytokine and nitric oxide secretion by rat alveolar macrophages after oral administration of bacterial extracts.

Oral administration of the bacterial immunomodulator Broncho-Vaxom (OM-85), a lysate of eight bacteria strains commonly causing respiratory disease, has been shown to enhance the host defence of the respiratory tract. In this study we examined the effect of orally administered (in vivo) OM-85 on stimulus-induced cytokine and nitric oxide secretion by rat alveolar macrophages in vitro. The results show that alveolar macrophages isolated from OM-85-treated rats secreted significantly more nitric oxide, tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta upon in vitro stimulation with lipopolysaccharide (LPS), whereas, in contrast, LPS-induced IL-6 secretion was significantly lower. The observed effects of in vivo OM-85 treatment on stimulus-induced cytokine secretion in vitro are not due to a direct effect of OM-85 on the cells, because in vitro incubation of alveolar macrophages with OM-85 did not result in altered activity, nor did direct intratracheal instillation of OM-85 in the lungs of rats result in altered alveolar macrophage activity in vitro. It is hypothesized that oral administration of OM-85 leads to priming of alveolar macrophages in such a way that immune responses are non-specifically enhanced upon stimulation. The therapeutic action of OM-85 may therefore result from an enhanced clearance of infectious bacteria from the respiratory tract due to increased alveolar macrophage activity.

Animals↗
PubMed1995

Chronic proliferative dermatitis in mice: neutrophil-endothelium interactions and the role of adhesion molecules.

The murine chronic proliferative dermatitis mutation (cpdm/cpdm) is characterized by epidermal hyperplasia and hyperproliferation of ventral and dorsal skin sites. The expression of endothelium-associated adhesion molecules was studied in combination with the binding capacity of various cell types on frozen sections of the affected skin. In correlation with the relative absence of lymphocytes in the cpdm/cpdm skin no lymphocyte binding could be observed, but avid adhesion of neutrophils was seen. Binding of neutrophils could be blocked with antibodies against L-selectin, LFA-1, CR3 and anti ICAM-1. No expression of vascular addressins or E-selectin on endothelium in the dermis was found. The cpdm/cpdm mutation has therefore characteristics of a psoriasis-like as well as a more generalized inflammatory skin condition.

Animals↗
PubMed1995

Acute stress affects cytokines and nitric oxide production by alveolar macrophages differently.

The production of cytokines by alveolar macrophages was studied after exposure of rats to an acute stress paradigm (mild inescapable footshocks). When alveolar macrophages from nonstressed animals were isolated and cultured, they readily produced interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) after stimulation with lipopolysaccharides (LPS). For these cytokines the dose response relationship for LPS was clearly biphasic. Nitric oxide (NO) production could only be detected upon LPS stimulation and seemed to be monophasic. However, when the animals were exposed to the acute stress paradigm, isolated alveolar macrophages (AM) showed a marked increase of IL-1 beta and TNF-alpha secretion upon LPS stimulation in vitro, but no changes in the production of IL-6 were detected. In contrast, exposure to the stress paradigm resulted in a strong decrease in NO production. The results indicate that emotional stress can rapidly induce altered behavior of AM, which is discussed in view of the important role these cells play in the regulation of the local immune responses in the lungs and the possible contribution to asthma.

Acute Disease↗
PubMed1995

Expression of the mucosal vascular addressin, MAdCAM-1, on sinus-lining cells in the spleen.

The MAdCAM-1 adhesion molecule is involved in lymphocyte homing into mucosal sites and is expressed on high endothelial venules of Peyer's patches and mesenteric lymph nodes. In the spleen, where high endothelial venules are absent, expression can be found on cells in the marginal zone between red and white pulp. By immunohistochemistry and electron microscopy it was demonstrated that in the spleen cells expressing MAdCAM-1 belong to the population of sinus-lining cells and that the expression is restricted to the sinus-lining cells closest to the lymphoid white pulp. Lymphocytes that migrate from the blood into this white pulp area will have to pass through the rim of cells expressing MAdCAM-1. A functional role for MAdCAM-1 or its lymphocyte ligand, the alpha 4 beta 7 integrin complex, was investigated by in vivo short-term homing experiments with anti-MAdCAM-1 and anti-alpha 4 beta 7 antibodies, but no direct role for this receptor-ligand interaction could be demonstrated.

Animals↗
PubMed1994

The role of the spleen in the organ-specific metastasis of murine BW 5147 T lymphomas.

Organ-specific metastasis of tumour cells may result from selective invasion and growth or from selective host cell responses. The present study demonstrates how selective interactions with the host affect the metastatic pattern of two murine T cell hybridoma lines, derived from the BW 5147 thymoma. Upon intravenous inoculation into syngeneic mice BW-14 cells preferentially colonize the kidneys, whereas BW-19 cells metastasize mainly to the spleen and the liver. The organ-specific behaviour of the two cell lines appears to be determined by a differential interaction with the spleen microenvironment. Inoculation of BW-14 cells into splenectomized mice results in increased liver colonization, indicating a negative effect of the spleen on BW-14 tumour development in the liver. Macrophages are likely to be involved in this inhibition, since inoculation of BW-14 cells into macrophage-depleted mice also leads to increased liver and spleen metastasis. In contrast, inoculation of BW-19 cells into splenectomized mice results in decreased liver metastasis, which indicates that the spleen exerts a stimulating effect on BW-19 cells. Macrophages also appear to be involved in this stimulation, since macrophage depletion causes a similar decrease in liver and spleen colonization. Hence components of the splenic microenvironment, probably macrophages, exert inhibiting or stimulating activities on BW-14 or BW-19 cells respectively, thereby determining the subsequent liver or kidney colonization.

Animals↗
PubMed1994

Macrophage subpopulations in the mouse spleen renewed by local proliferation.

A dual origin, by both immigration of blood monocytes and local proliferation has been reported for macrophages, which are heterogeneous in several aspects. Until now few studies have focussed on renewal of macrophages. Therefore, in this study macrophage renewal by local proliferation has been studied in the spleen. Spleen tissue of mice which had received BrdU intravenously was investigated immunohistochemically to detect BrdU incorporated by macrophages. BrdU incorporation by splenic macrophages was studied under steady state conditions as well as during repopulation after experimental macrophage depletion. Under steady state conditions, BrdU incorporation was found in 3.0 +/- 0.5% of the white pulp macrophages and in approximately 1% of the metallophilic macrophages only. Comparable results were found during repopulation after experimental macrophage depletion. The data suggest that renewal of macrophages by local proliferation is restricted to certain subsets in the spleen and that the macrophage subsets of the spleen are renewed by different mechanisms, or belong to different lineages of macrophage differentiation.

Animals↗
PubMed1994

The role of sialic acid in the localization of lymphocytes in the spleen.

The role of carbohydrate structures in the interaction of lymphocytes and endothelial cells is well established. Here the influence of sialic acid in the entrance and localization of lymphocytes in the lymphoid white pulp area of the spleen was studied by injecting sialidase in vivo. A role for sialic acid molecules on stromal elements of the spleen was determined. Although the identity of the cells that bear sialidase sensitive receptors could not be established, a role for marginal zone macrophages could be ruled out by macrophage depletion studies.

Animals↗
PubMed1994

Activation of high endothelial venules in peripheral lymph nodes. The involvement of interferon-gamma.

The introduction of Freund's complete adjuvant into footpads of mice leads to functional changes of the high endothelial venules (HEV) in the draining lymph nodes. Using an in vitro adhesion assay, increased binding of monocytes and dendritic cells could be seen. These effects are also seen after injection of high doses of INF-gamma. No changes in the expression of vascular addressins, VCAM-1, E selection or ICAM-1 could be observed but the binding of monocytes could be blocked with an antibody against Mac-1. Depletion studies have made it clear that macrophages in the lymph node are not directly involved in the activation of the HEV. The induction of additional adhesion mechanisms on HEV could be an efficient way to recruit inflammatory cells into the lymph node, thereby regulating the local immune response.

Animals↗
PubMed1994

Non-sensitizing epicutaneous skin tests prevent subsequent induction of immune tolerance.

Oral administration of nickel or chromium to naive guinea pigs results in immune unresponsiveness to subsequent induction of allergic contact hypersensitivity. Such "oral tolerance" depends on the oral dose, is antigen specific, T-suppressor-cell mediated, and very persistent. In contrast, oral antigen administration to sensitized animals results at best in transient desensitization. Here we report that even non-sensitizing epicutaneous skin contacts prevented the subsequent induction of oral tolerance. These data support the view that primed T cells are less sensitive to suppressor T-cell function than naive T cells.

Administration, Oral↗
PubMed1994

Antigen-bearing Langerhans cells in skin draining lymph nodes: phenotype and kinetics of migration.

Application of the fluorescent contact sensitizer Rhodamin B on mouse epidermis was used to study the migration kinetics of Langerhans cells into the draining lymph nodes. The expression of the dendritic cell markers NLDC-145 and MIDC-8 was followed over time to determine the correlation between these markers and Langerhans cell migration. In contrast with its high expression on intraepidermal Langerhans cells, the expression of NLDC-145 on dendritic cells in the draining lymph node was low at 24 h but increased at later times; in contrast, MIDC-8 expression on dendritic cells decreased. Ten days after Rhodamin B application, antigen-bearing Langerhans cells were still present in the epidermis; application of another unrelated contact sensitizer to the epidermis at this time did not lead to migration of these residual Langerhans cells. These results indicate that not all antigen-bearing Langerhans cells migrate from the skin after application of a contact sensitizer, indicating that signals in addition to simple antigen binding are necessary for migration. During this migration from epidermis to lymph nodes Langerhans cells undergo phenotypic changes. The decreased expression of the endosomal antigens MIDC-8 and MOMA-2 correlates with differentiation from predominantly antigen-processing cells to predominantly antigen-presenting cells. The reduced expression of NLDC-145 is discussed in light of a Langerhans cell-independent pathway of antigen transportation from skin to lymph node.

Animals↗
PubMed1994

Immunohistological and functional analysis of adhesion molecule expression in the rheumatoid synovial lining layer. Implications for synovial lining cell destruction.

OBJECTIVE: It has previously been shown that the adhesion of lymphocytes to microvascular endothelium mediates lymphocyte extravasation within inflamed synovium. After passing the endothelial barrier, binding of lymphocytes to matrix proteins and synovial lining cells may further lead to synovial membrane hyperplasia and subsequent cartilage destruction. Thus, we have explored the molecular basis of T cell-synovial lining cell interaction in the synovial membrane of patients with rheumatoid arthritis (RA). METHODS: Using an immunohistochemical staining technique and an in vitro frozen section assay we studied the expression and the role of several adhesion molecules in T lymphocyte-synovial lining cell interaction in the inflamed synovial membrane. RESULTS: In RA the macrophage-like (type A) synovial lining cells express high levels of intercellular adhesion molecule 1 [ICAM-1 (CD54)], whereas the fibroblast-like (type B) synovial lining cells predominantly express vascular cell adhesion molecule 1 (VCAM-1), in addition to moderate levels of ICAM-1. Both cell types express low levels of fibronectin. Unstimulated and anti-CD3 stimulated peripheral blood T cells bear the respective ligands lymphocyte function associated antigen 1 [LFA-1 (CD18/11a)], and very late antigen 4 and 5 [VLA-4 (CD29/49d) and VLA-5 (CD29/49e)]. T lymphocytes predominantly bound to type B synovial lining cells. Inhibition studies with monoclonal antibodies revealed that this binding involves the VLA-4/VCAM-1 and VLA-5/fibronectin (FN), but not the VLA-4/CS1 pathway. LFA-1 is also involved in this interaction via its ligand ICAM-1. CONCLUSION: These results show that the molecular basis of T lymphocyte binding to rheumatoid synovial lining cells is different from that described for T lymphocyte binding to synovial membrane vascular endothelium which involves the VLA-4/VCAM-1 and VLA-4/CS-1 pathways, but not the LFA-1/ICAM-1 pathway.

Antibodies, Monoclonal↗