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D Leszczynski

Publications and source records attributed to D Leszczynski.

At least 37 records · Page 2Linked to original sources
PubMed1990

The frequency of B cells secreting antibodies against donor MHC antigens in rats rejecting renal allografts.

We have estimated the frequency of B cells secreting antibodies against donor MHC antigens in rats rejecting histoincompatible renal allografts. In a major plus minor antigen-incompatible DA-to-WF combination on day 4 post-transplantation, reverse protein A plaque assay demonstrated that in the graft the frequency of lymphoid cells secreting Ig was 1:850. A major locus-incompatible and minor locus-compatible, congeneic LBN-to-Lewis strain combination was then applied to estimate the specificity of the secreted antibody. The lymphoid inflammatory cells were fused with mouse myeloma cells, cultured under limiting dilution conditions, and assayed by ELISA to donor and irrelevant strain spleen cells. Among cells infiltrating the graft, the fusion frequency was 1:172 x 10(3) and the frequency of Ig-producing hybrids 1:400 x 10(3) (i.e., this assay was approximately three log orders less sensitive than the reverse pA assay). The frequency of hybridomas secreting specifics antibodies against donor MHC antigens was 1:720 x 10(3) (i.e., every second hybridoma deriving from inflammatory population produced specific Ig). In addition, there was at least one obviously polyspecific population of hybridomas, detectable only in the spleen and reactive with all rat strains tested with a frequency of 1:700 x 10(3). The inflammatory cells were also cultured directly under limiting dilution conditions, and the frequency of Ig-secreting cells was determined by ELISA. The frequency of inflammatory lymphocytes secreting detectable amounts of immunoglobulin in the supernatant was 1:14 x 10(3) in the graft (i.e., this assay was approximately one log order less sensitive than the reverse protein A plaque assay).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of granulocyte-macrophage colony stimulating factor on endothelial antigenicity.

We have investigated if recombinant granulocyte-macrophage colony stimulating factor (GM-CSF), alone or in concert with recombinant gamma interferon, affects the endothelial cell expression of class I major histocompatibility complex antigen. Results obtained show that the GM-CSF increases class I expression on the endothelial cell in a time- and dose-dependent manner. The effect of interferon gamma on class I expression is diminished in the presence of GM-CSF, cAMP, or prostaglandin E2, but is increased in the presence of cGMP. N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA 1004), an inhibitor of cAMP- and cGMP-dependent protein kinases, abolished GM-CSF-induced class I expression, while indomethacin increased it. When added to the endothelial cell cultures together with interferon gamma GM-CSF, HA 1004 as well as indomethacin abolished the inhibitory effect of GM-CSF on interferon gamma-induced class I expression. The results suggest that GM-CSF diminishes effect of interferon gamma on class I major histocompatibility complex expression on the endothelial cell by inducing production of rostacyclin. This, in turn, induces cAMP as a second messenger, which then leads to the events inhibiting expression of class I major histocompatibility complex antigen.

Animals↗
PubMed1990

Properties of B cells and Thy-1-antigen-expressing cells infiltrating rat renal allografts.

We have examined (1) the frequency of B cells secreting antibodies against donor major histocompatibility complex (MHC) antigens and (2) the properties of Thy-1-antigen-expressing leukocytes in rats rejecting renal allografts. Our results show that B cells secreting antibodies are present in the inflammatory cell population at the frequency of 1:850. Among them only 1 out of 2-150 is engaged in production of antibodies directed to the graft MHC antigens, depending on the method of assay. This suggests that despite the observed significant production of nonspecific immunoglobulin in situ, only a minority of the B-cell population is specifically committed to the graft MHC antigens. This finding is concordant with the described previously low frequencies of the T cells specifically directed toward the graft MHC antigen. The role of the "immunologically noncommitted" cells in graft rejection is unknown. We have found that a substantial part (up to 60%) of inflammatory cells invading a rat kidney allograft express the Thy-1 antigen. This suggests that they might be immature (progenitor?) cells and, therefore, unable to respond to the graft antigens. Progenitor-like properties of these cells have been confirmed by their ability to reconstitute lethally irradiated syngeneic rat. Finally, these immature cells are of lymphoid, not of myeloid, linkage, because they do not proliferate in the presence of GM-CSF.

Animals↗
PubMed1990

Interleukin-1 alpha inhibits the effects of gamma-interferon and tumor necrosis factor alpha on the expression of the major histocompatibility antigens by the rat endothelium.

Modulation of the major histocompatibility (MHC) antigen expression on rat endothelial cells by a mixture of cytokines has been examined. Experiments were performed employing both enzyme-linked immunoassay (ELISA) and fluorescence-activated cell-sorting (FACS) techniques and recombinant cytokines: interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), and gamma-interferon (tau IFN). The results obtained show that TNF alpha enhances the effect of tau IFN on the expression of class I and II MHC antigens. IL-1 alpha did not affect tau IFN-induced class I expression but did inhibit tau IFN-induced class II expression. Finally, TNF alpha-induced class I MHC expression was inhibited strongly by IL-1 alpha. Pretreatment of endothelium with tau IFN did not potentiate the effects of IL-1 alpha or TNF alpha on the endothelial MHC antigen expression. These results suggest a possible anti-inflammatory role of IL-1 alpha via down-regulation of MHC antigen expression by the endothelium.

Animals↗
PubMed1989

Eicosanoids are regulatory molecules in gamma-interferon-induced endothelial antigenicity and adherence for leucocytes.

When the endothelial cells (ECs) were stimulated with gamma-interferon (gIFN) in the presence of methylprednisolone (MP) or prostaglandin E2 (PGE2), MP enhanced gIFN-induced Ia antigen expression, whereas PGE2 inhibited it. On the other hand, while PGE2 had no effect on leucocyte binding to ECs, MP entirely inhibited it. By using selective inhibitors of the cyclo-oxygenase pathway (indomethacin, IM) and the 5-lipoxygenase pathway (L651.392), we found that addition of IM to gIFN-stimulated ECs enhanced Ia expression but had no effect on leucocyte adherence to ECs. Instead, addition of L651.392 to gIFN-stimulated ECs partially reduced leucocyte adherence to ECs but had no effect on Ia expression. Pretreatment of the ECs or leucocytes or both with monoclonal anti-class II antibody, had no effect on gIFN-induced leucocyte binding to ECs. These findings suggest that gIFN-induced endothelial cell antigenicity and leucocyte adherence are regulated independently of each other by different molecular pathways. Moreover, arachidonic acid metabolites appear to be the regulatory molecules in gIFN effects on the ECs.

Animals↗
PubMed1989

Local events in graft rejection.

It appears that allograft rejections can be considered as a series of cellular and molecular cascades of inflammation triggered by the immune response. In acute rejection, inflammatory changes with a prominent blast cell component dominate. The main result is toxic damage of several parenchymal components, particularly the microvascular endothelium, resulting in necrosis of the parenchyma and loss of the allograft within days after transplantation. In the chronic type of rejection, inflammation also exists, but the major manifestations are different. Adventitial inflammation and perivascular cuffing of leukocytes result in concentric intimal proliferation and atherosclerosis. Very little experimental data exist, at present, on the mechanisms of transplant atherosclerosis and chronic rejection.

Acute Disease↗
PubMed1988

Leukotriene B4 increases the lymphocyte binding to endothelial cells.

Leukotrienes are potent mediators of local microvascular environment. Leukotriene B4 treatment of cultured endothelium increases the binding of lymphocytes to endothelial cell monolayers within minutes. This effect is dose-dependent and reversible upon removal of the leukotriene. Pretreatment of lymphocytes slightly decreases the binding and pretreatment of both lymphocytes and endothelium with leukotriene B4 prior to the adherence assay did not alter the binding. These results suggest that leukotriene B4 regulates exclusively the vascular side, but not the white cell side of this interaction.

Animals↗
PubMed1987

Renal target structures in acute allograft rejection: a histochemical study.

With an aim to investigate the relative sensitivity of various renal structures to allograft rejection, we analyzed the histochemical reaction intensity of seven enzymes prominently displayed in various rat kidney components, and correlated the expression of these enzymes both to the degree of intra-graft inflammation and to the expression of class II MHC antigens in graft capillary endothelial cells. Syngeneic transplants and normal renal tissue were used as controls. At the peak of inflammation, on the fifth day after transplantation, adenosine triphosphatase activity of vascular endothelial cells was strongly reduced in the peritubular capillary endothelium of the allograft, moderately in the glomerular endothelium but very little in the endothelium of arteries and veins. Lactate dehydrogenase, succinate dehydrogenase, isocitrate dehydrogenase, alkaline phosphatase, acid phosphatase and glucose-6-phosphatase activities were moderately reduced in the proximal tubular cells of the allograft and even less in the distal tubular cells. The results suggest that the prime target of the host immune attack is the intertubular capillary endothelium, whereas the distal tubular cells are relatively insensitive to immune injury.

Acute Disease↗
PubMed1987

Impact of class II major histocompatibility complex antigen expression on the immunogenic potential of isolated rat vascular endothelial cells.

We have investigated the immunogenic potential of rat heart vascular endothelial cells by their ability to induce an accelerated rejection of a relevant heart allograft, and related the immunogenic potential to the expression of class II major histocompatibility complex (MHC) antigens on the endothelial cell surface. Only 12% of freshly isolated rat vascular endothelial cells express class II antigens in serum-free medium, and the level of expression is low as judged by immunoperoxidase staining and/or the ability of endothelial cells to bind staphylococci to the cell surface after treatment with monoclonal antibodies to the class II molecule. On the other hand, 99% of the endothelial cells under the same conditions express class I, and the level of expression is high. The class II antigen expression of vascular endothelial cells can be upregulated to more than 98% by recombinant gamma-interferon in vitro--and, concomitantly, the level of expression becomes high, even on the cell surface. Treatment with gamma-interferon did not substantially alter the level of class I expression. The endothelial cells expressing class II antigens weakly, are also weakly immunogenic in vivo: 10(7) endothelial cells are required to reduce the graft survival by 50% of that of the unprimed host. On the contrary, the endothelial cells of the same lineage induced to express class II antigens by gamma-interferon in vitro are highly immunogenic in vivo, as immunogenic as freshly-isolated spleen dendritic cells: only 10(4) endothelial cells are required to induce a 50% reduction of graft survival. These observations demonstrate for the first time that rat vascular endothelial cells are immunogenic in a primary transplantation response in vivo--and, moreover, that the immunogenic capacity of the endothelial cells is directly proportional to the extent of class II MHC antigen expression on the cell surface.

Animals↗
PubMed1987

Evidence that thymectomized, bone marrow-reconstituted rats do not reject their allografts.

We have investigated the reasons why thymectomized, bone marrow-reconstituted (B) rats do not reject their allografts, by comparing the structure of inflammation and functions of inflammatory cells in nonrejecting allografts to rejecting allografts in normal control recipients. The results demonstrate that B recipients mount a specific cellular response towards the graft. The response in B recipients differs from that in normal controls by a smaller intensity of inflammation, fewer blast cells, and activated mononuclear phagocytes in the inflammatory infiltrate, as well as a delay in the appearance of specific donor-directed lytic activity in the graft. B rats also have fewer blast cells and an inverted CD4/8 ratio in the spleen. There is no obvious absence of any given cell type or cellular function in the graft inflammatory infiltrate. In light of these results no cell type responsible for allograft nonrejection can be pinpointed.

Animals↗