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R Renkonen

Publications and source records attributed to R Renkonen.

At least 91 records · Page 5Linked to original sources
PubMed1990

Characterization of high endothelial-like properties of peritubular capillary endothelium during acute renal allograft rejection.

Acute allograft rejection is characterized by leukocyte infiltration. Previously we suggested that the site of entry of lymphocytes into rejecting kidney allografts is the peritubular but not other capillary endothelium. Here we confirm this observation in a frozen section ex vivo binding assay and further characterize the peritubular capillary endothelium during acute kidney allograft rejection. The increase in lymphocyte binding to peritubular capillaries precede the peak of inflammation (leukocyte accumulation) in the graft. Pretreatment of lymphocytes with antibodies against CD 11a and CD 18 (LFA-1 alpha and beta chain, respectively) could decrease the lymphocyte binding, whereas ICAM-1 pretreatment of tissue sections was ineffective. Light- and electromicroscopy revealed a marked activation of peritubular capillary endothelial cells in allografts, whereas these alterations were less severe or absent in syngeneic controls and normal kidneys. Finally our data suggest that the ligand responsible for the binding of lymphocytes to kidney peritubular areas is organ specific. Only mannose-1 phosphate, but not mannose-6 phosphate, could decrease the lymphocyte binding. Y-1, an antibody staining rat lymph node high endothelial venules (HEV), did not react with allograft peritubular capillaries having functional and morphologic similarities to HEV.

Animals↗
PubMed1989

Protein kinase C is crucial in signal transduction during IFN-gamma induction in endothelial cells.

We have demonstrated that IFN-gamma, a potent peptide mediator in inflammatory responses, operates via the protein kinase C dependent transduction pathway in the induction of class II MHC antigens on rat microvascular endothelial cells. Stimulators of protein kinase C, like PMA, replaced IFN-gamma in the induction of MHC class II on endothelial cells in a dose-dependent manner. Selective enzyme inhibitors of protein kinase C, H-7 as well as sphingosine down-regulated the IFN-gamma induced class II expression in a dose-dependent manner. Addition of cAMP or cGMP in the culture, had no effect on the class II expression on the endothelial cells. Transient rise of cytosolic Ca2+ by calcium ionophore A23187, or a calmodulin antagonist W-7, had no effect on the IFN-gamma induced class II expression.

Animals↗
PubMed1989

Lymphokine-activated killer (LAK) activity to cultured rat kidney parenchymal components in vitro.

The susceptibility of cultured rat kidney parenchymal components to natural killer (NK) cell and lymphokine-activated killer (LAK) cell-mediated lysis in a 4-h in vitro 51chromium assay was investigated. Large granular lymphocytes (LGL) in the spleen and in the kidney allograft were able to lyse YAC cells during rejection, but they did not damage target endothelial, glomerular mesangial, glomerular epithelial, or tubular cells in resting state. Stimulation of the target cells with gamma-interferon - known to induce MHC (class II) antigens on the target cell surface - did not make the target cells susceptible to NK-mediated lysis. LAK cells generated by a 3-day incubation with interleukin-2 (IL-2) effectively lysed both YAC and P815 target cell lines. LAK cells were also slightly cytotoxic to all tested parenchymal target components in resting state. Gamma-interferon treatment of the cultured parenchymal cells prior to the chromium release assay, however, reduced LAK-mediated parenchymal cell cytotoxicity to nearly nondetectable levels. Obviously, many lymphokines, including IL-2 and gamma-interferon, are produced during rejection at the site of inflammation. This might induce the generation of LAK cells in situ as the lymphokines induce the production of MHC antigens in the graft. We interpret these findings as indicating that regardless of the generation of LAK, the protective effect of gamma-interferon neutralizes the LAK effect, and we suggest that neither LGL nor LAK cells play any essential role in rat kidney allograft rejection.

Animals↗
PubMed1989

Gamma-interferon induces prostacyclin and prostaglandin but not lipoxygenase product synthesis in rat endothelial cells.

The major arachidonic acid metabolites excreted by untreated rat heart endothelial cells were prostacyclin (PGI2), 5-hydroxyeicosatetraenoic acid (5-HETE) and 15-hydroxyeicosatetraenoic acid (15-HETE). Trace amounts of both prostaglandin E (PGE) and thromboxane B2 (TXB2) were also produced. The activity of leukotriene B4 (LTB4) was the same as baseline activity. Gamma-interferon (gamma-IFN) treatment increased the production of PGI2 and PGE more than three-fold compared to control values. Thromboxane production increased two-fold while the excretion of 5-HETE and 15-HETE was unaffected. No LTB4 excretion was seen after gamma-IFN stimulus. Methylprednisolone downregulated the 5-HETE, 15-HETE and prostacyclin production both in normal and gamma-IFN treated cells. Indomethacin decreased prostacyclin excretion in untreated cells and also decreased gamma-IFN-induced prostacyclin and PGE excretion. Taken together these results indicate that rat microvascular endothelial cells excrete prostaglandins and prostacyclin, but not leukotrienes.

Animals↗
PubMed1989

Site of influx of inflammatory white cells into a rejecting rat renal allograft.

In this paper we demonstrate that the vascular endothelium of a normal kidney and a syngeneic kidney graft binds only poorly syngeneic or allogeneic lymphocytes in an in vitro binding assay. On the contrary, the peritubular capillary endothelium of an allograft binds almost 7 times more lymphocytes than the peritubular capillary of a normal kidney. These findings suggest that the site of influx of inflammatory capillary white cells into the graft during rejection is the peritubular capillary endothelium.

Animals↗
PubMed1989

Monitoring of bone marrow transplant recipient liver by fine-needle aspiration biopsy.

Acute graft-versus-host disease (aGVHD) of the liver was studied with fine-needle aspiration biopsies of thirty-four bone marrow transplant recipients. White cell differentials of liver FNABs and simultaneously taken blood samples were performed, and the increment and corrected increment methods were used to quantitate the inflammatory reaction in the liver. Biopsies taken before transplantation were used as the baseline. During aGVHD, the percentage of lymphoid cells and monocytes increased in the liver. The appearance of immunological blasts, together with a high proportion of activated lymphocytes in the FNABs, were typical findings during aGVHD. In patients with apparent prolonged liver graft-versus-host disease small lymphocytes were the predominating cell type. After initiating corticosteroid treatment, the number of blasts and the proportion of activated lymphocytes decreased. There was no significant difference in the proportions of CD4- and CD8-positive lymphoid cells in FNABs during or after aGVHD.

Acute Disease↗
PubMed1989

Regulation of intercellular adhesion molecule-1 expression on endothelial cells with correlation to lymphocyte-endothelial binding.

Intercellular adhesion molecule-1 (ICAM-1) expression on cultured human umbilical cord vein endothelial cells (EC) and its correlation to the leucocyte adherence to EC was investigated. Gamma interferon (IFN-gamma) increases the ICAM-1 expression on EC and concomitantly also increases the binding of leucocytes to EC in vitro. Methylprednisolone down-regulates the IFN-gamma-induced binding, but does not alter the ICAM-1 expression. Leukotriene B4 (LTB4) rapidly increases the binding of lymphocytes to EC, but does not induce ICAM-1 expression on the EC. The dissociation between ICAM-1 expression and leucocyte binding to EC clearly indicates that ICAM-1 is not the only ligand.

Antigens, Differentiation↗
PubMed1989

Lymphocyte binding to and penetration through vascular endothelium is stimulated by platelet-activating factor.

Lymphocytes have an important role in acute inflammatory reactions such as acute allograft rejection. Recirculating lymphocytes attach to vascular endothelium and penetrate through it into tissue parenchyma. Many recent studies have shown that different protein mediators, like gamma interferon, interleukin 1, and tumour necrosis factor enhance lymphocyte binding to and penetration through the endothelium, i.e. lymphocyte homing. We investigated the effect of platelet-activating factor (PAF) in lymphocyte binding and penetration in vitro. Treatment of rat heart microvascular endothelial monolayers with PAF (10(-6)-10(-10) M) increased the lymphocyte binding up to 1.6-fold. The effect is dose- and time-dependent. The PAF effect was reversible upon removal of the agonist: 60 min after removal of PAF no increase in the lymphocyte binding was detected. Pretreatment of endothelial cells, lymphocytes, or both of these cell types led to an increase in lymphocyte binding to endothelial monolayers. The effect of PAF in lymphocyte penetration through endothelium was investigated by using endothelial cell monolayers cultured on top of millipore filters. An optimal PAF dose (10(-8) M) for 10 min increased the number of lymphocytes penetrating through the endothelial cell monolayer into the filter by a factor of 3. These results suggest that PAF has no important role in lymphocyte homing, since it can activate the endothelial cells, the lymphocytes, or both cell types.

Animals↗
PubMed1989

Bone marrow transplantation in the rat. Lytic functions of inflammatory leukocytes during acute graft-versus-host disease.

We have isolated inflammatory leukocytes from various lymphoid and parenchymal organs after total body irradiation and bone marrow transplantation from either an allogeneic or syngeneic strain and tested their ability to perform lytic functions in vitro. No direct lytic activity (i.e. cytotoxic T lymphocytes, CTL) to relevant strain-derived target cells in the lymphoid or parenchymal target organs was seen preceding or during acute graft-versus-host disease (aGVHD). Instead, the leukocytes of the spleen and blood and the inflammatory cells of liver and lungs were efficient effector cells against recipient-derived target cells in the presence of relevant antibody (antibody dependent cellular cytotoxicity, ADCC). The NK activity against YAC-1 (natural killer, NK) target cells was first high in the spleen, but when the aGHVD appeared in the allograft marrow recipients the NK activity decreased in the spleen with a concomitant increase in the liver, but not in the other parenchymal target organs. At the same time no NK activity was seen in the syngeneic marrow graft recipients' parenchymal organs. These observations suggest functional differences in the structure of inflammation in the different target organs of aGVHD.

Acute Disease↗
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↗
PubMed1988

Interferon-gamma protects human endothelial cells from lymphokine-activated killer cell-mediated lysis.

In adoptive immunotherapy the lymphokine-activated killer (LAK) cells, known to be cytotoxic to many tumor cell lines, are injected i.v. into tumor-bearing animals or cancer patients. However, in addition to a significant reduction in tumor masses, complications occur in many cases, most severe of which are the vascular leak syndrome and hypotension. In this report we show that LAK cells are also cytotoxic to normal vascular endothelial cells, which may partly contribute to these complications. Incubation of the endothelial cells with interferon-gamma (IFN-gamma), but not with interleukin 1 (IL 1) or tumor necrosis factor, protects the endothelial cells from LAK-mediated lysis in a dose- and time-dependent manner. The protective effect is abolished by monoclonal antibody against IFN-gamma. However, the IFN-gamma treatment does not protect LAK-sensitive tumor cell lines from LAK-mediated lysis. Concomitantly IFN-gamma also induces both class I and class II antigens on endothelial cells. The induction of these major histocompatibility complex (MHC) antigens does not explain the protective effect: timewise, the protection is complete already within 24 h after addition of IFN-gamma to endothelial cell culture, whereas the induction of MHC antigens peaks at 72 h, and antibodies against these antigens are not able to abolish the protective effect.

Antibodies, Monoclonal↗
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↗