Search PubMed⌕ Search

Biomedical subjects

G Kaplanski

Publications and source records attributed to G Kaplanski.

At least 73 records · Page 4Linked to original sources
PubMed1994

Interleukin-1 induces interleukin-8 secretion from endothelial cells by a juxtacrine mechanism.

Inflammation is characterized by migration of neutrophils through the endothelium, and the chemokine interleukin-8 (IL-8) appears to be involved. We asked whether adherence of cells bearing a membrane-form of interleukin 1 (IL-1) induces IL-8 secretion from human umbilical vein endothelial cells (HUVEC) and fibroblasts. Human peripheral blood mononuclear cells (PBMC) were stimulated with endotoxin for 12 hours and then fixed for 4 hours with paraformaldehyde. When these cells were added to HUVEC or fibroblasts, IL-8 production was induced. This stimulation by fixed PBMC was attributed to IL-1, because pretreatment of HUVEC or fibroblasts with IL-1 receptor antagonist (IL-1Ra) reduced the induction by 95% and 80%, respectively, P < .005. Using anti-IL-1 alpha monoclonal antibodies, reduction was complete, whereas anti-IL-1 beta had no effect. IL-1 alpha was shown on the surface of monocytes by fluorescence-activated cell sorter (FACS) analysis. Blockade of IL-1 receptors on PBMC did not affect the activity of membrane-associated IL-1 alpha, indicating that IL-1 is not anchored to the membrane through its receptors. However, PBMC treated with D-mannose before fixation resulted in a loss of activity; this loss of activity was associated with release of IL-1 alpha, not IL-1 beta, into the supernatant. Thus, anchoring of IL-1 alpha to the membrane may be via a lectin or mannose receptor-like interaction. Blockade of membrane IL-1 alpha required a 30-fold and fivefold excess of IL-1Ra compared with the amount required to block soluble IL-1 beta and IL-1 alpha, respectively. We conclude that the fixed PBMC IL-8 inducing activity is almost entirely caused by IL-1, that this represents IL-1 alpha bound to a surface lectin or mannose receptor on the monocyte, and that it functions in inflammation via juxtacrine interactions.

Cell Membrane↗
PubMed1994

Interleukin-1 receptor blockade reduces the number and size of murine B16 melanoma hepatic metastases.

Hepatic metastasis in melanoma is affected by processes of tumor cell adhesion to sinusoidal cells, avoidance of cytotoxic cells, and local growth-promoting activity. A role for interleukin-1 (IL-1) in these events was evaluated in vitro and in vivo by specifically blocking IL-1 receptors using the naturally occurring IL-1 receptor antagonist (IL-1Ra). At 10- and 100-fold molar excess, IL-1Ra reduced the IL-1-mediated adhesion of B16 melanoma cells to cultured hepatic sinusoidal endothelial cells by 60 and 100%, respectively. Conditioned media derived from murine hepatic sinusoidal endothelial cells contain growth-promoting activity for B16 cells, and IL-1 increased its production 2.5-fold (P < 0.01). The addition of IL-1Ra to sinusoidal cells reduced the spontaneous release of the growth-promoting activity by 32% (P < 0.05). In addition, blocking IL-1 receptors on melanoma cells reduced their responsiveness to endothelial-conditioned medium (P < 0.05). A single dose of IL-1Ra (0.5 mg/kg) given to mice i.p. 2 h prior to intrasplenic injection of melanoma cells reduced the number of hepatic metastases by 50% and the metastatic volume by 70% compared to vehicle-injected controls (P < 0.01). When given 2, 4, and 6 days after the injection of tumor cells, IL-1Ra reduced the volume of metastases by 58% (P < 0.01). Fifty % of mice pretreated with 0.5 mg/kg IL-1Ra and given 3 additional doses on days 2, 4, and 6 died after 13.5 +/- 0.4 days compared to 11.3 +/- 0.2 days for controls (P < 0.01). In mice pretreated and given 10 daily doses at 5 mg/kg, there was an 80% reduction in hepatic metastases. Using this regimen, survival was 18.1 +/- 2.4 days in the IL-1Ra group and 11.2 +/- 1.5 in controls (P < 0.001). These studies demonstrate a significant role for IL-1 in implantation and growth of metastatic melanoma in the liver.

Animals↗
PubMed1994

Long-term results of therapy with interferon alpha for cryoglobulinemia associated with hepatitis C virus infection.

We describe the long term results of treatment with interferon (IFN) in two patients with cryoglobulinemia and chronic hepatitis related to Hepatitis C virus (HCV). Our results suggest that interferon may induce long remission in cryoglobulinemia associated with HCV infection and that the effect of IFN is not dependent on the effect on liver function, but results of its antiviral activity.

Aged↗
PubMed1994

Accelerated hypertension and nephroangiosclerosis associated with antiphospholipid syndrome. Report of two cases and review of the literature.

We describe two patients with the primary antiphospholipid syndrome who presented with severe hypertension. Renal biopsy specimen provided histologic evidence of intra-renal vascular disease with intravascular microthrombosis and nephrosclerosis, without feature of proliferative glomerulopathy. Accelerated hypertension and nephroangiosclerosis might indeed be one of the complications associated with anticardiolipin antibodies. The mechanism responsible might be the interaction of anticardiolipin antibodies, platelets and endothelial cell leading to microthrombi formation and increased local mitogenic activity that attract and stimulate neighbouring smooth muscle cell and fibroblast proliferation.

Adult↗
PubMed1994

Secondary pancreatic involvement of mycosis fungoides detected by a clinically palpable mass.

A patient with a 4-year history of mycosis fungoides, who presented a pancreatic spreading of the disease, detected by a clinically palpable mass, is reported and discussed with a review of the literature. Mycosis fungoides (MF) is a T cell lymphoma primarily localized to the skin. Laparoscopic staging and autopsy studies, however, have shown that lymph node involvement or visceral spreading is common in the course of the disease [1-3]. Among visceral manifestations of MF, pancreas infiltration is found in 20-40% of autopsied cases [1, 2, 4]. Occurrence of a palpable pancreatic mass has never been described. We report a patient with a long-standing MF, and a secondary pancreatic extension detected by a palpable mass.

Aged↗
PubMed1994

A novel role for E- and P-selectins: shape control of endothelial cell monolayers.

The migration of neutrophils from blood vessels to peripheral tissues is a key step of inflammation. This requires the formation of transient gaps between endothelial cells with concomitant leucocyte squeezing through these narrow apertures and immediate restoration of endothelium continuity. It is currently considered that the main role of selectins is to mediate the initial contact between flowing leucocytes and endothelial cells. We show here that the binding of E- or P-selectins by specific antibodies induces a marked 'rounding up' of interleukin-1- or thrombin-activated human endothelial cells, respectively. Also, anti-E-selectin antibodies trigger a transient increase in cytosolic calcium involving intracellular calcium stores. No such effect is observed when von Willebrand factor or intercellular adhesion molecule 1 are similarly bound. Thus, in addition to promoting the initial interaction between activated endothelium and moving leucocytes, selectins might play a role in the induction of subsequent endothelial deformation, which would facilitate leucocyte arrest and transmigration towards peripheral tissues, and enhance the diffusion of soluble molecules between intravascular and peripheral compartments. Our results are consistent with this hypothesis and demonstrate a new property of endothelial selectins.

Antibodies, Monoclonal↗
PubMed1993

Intravenous endotoxin suppresses the cytokine response of peripheral blood mononuclear cells of healthy humans.

When administered parenterally, endotoxin stimulates the synthesis of IL-1, TNF-alpha, and IL-6. However, this initial injection induces tolerance; a second injection of endotoxin results in lower levels of circulating cytokines. In our study, five healthy male volunteers between the ages of 18 and 30 were injected with Escherichia coli endotoxin. Four subjects received only saline. Immediately before the injection and 3, 6, and 24 h afterward, PBMC were isolated and stimulated in vitro with endotoxin, IL-1, or toxic shock syndrome toxin-1. Inasmuch as CD14+ monocytes are the primary source of the cytokines induced by these stimuli, results are expressed as cytokine production per 10(6) CD14+ cells. Six h after endotoxin injection, endotoxin-stimulated CD14+ cells synthesized 66% less IL-1 beta (p < 0.01), 47% less TNF-alpha (p < 0.001), 56% less IL-6 (p < 0.01), and 49% less IL-8 (p < 0.01) than cells obtained before the injection. This suppression was not specific for endotoxin; IL-1 beta-induced IL-1 alpha and TNF-alpha were reduced by 84% (p = 0.01) and 68% (p < 0.001), respectively. A decrease in cytokine synthesis was also observed using toxic shock syndrome toxin-1 as a stimulus: 57% for IL-1 beta (p = 0.06), 70% for TNF-alpha (p < 0.01), 56% for IL-6 (p < 0.05), and 71% for IL-8 (p = 0.001). When data were expressed as cytokine production per 10(6) PBMC, cells isolated 3 h after endotoxin injection synthesized significantly less stimulus-induced IL-1, TNF-alpha, IL-6, and IL-8 than did PBMC from saline-injected controls. We conclude that endotoxin tolerance is due, in part, to changes in the stimulus-induced cytokine response of circulating CD14+ cells.

Antigens, CD↗
PubMed1993

Activated platelets induce endothelial secretion of interleukin-8 in vitro via an interleukin-1-mediated event.

Migration of neutrophils through endothelial cells (EC) and induction of cytokine secretion are two well-documented events during the inflammatory reaction. The inflammatory, chemotactic cytokine interleukin-8 (IL-8) is secreted by EC in response to IL-1 stimulation. In this study, we show that platelets activated with either adenosine-5'-diphosphate or epinephrine induce IL-8 secretion by EC. This stimulatory activity was found to be associated with sedimented platelets after activation. Blockade of IL-1 receptors on EC with IL-1 receptor antagonist (IL-1Ra) decreased the stimulatory effect of whole activated platelet preparations by 59% (P < .05). Similarly, IL-1Ra pretreatment of EC reduced the stimulatory effect of sedimented activated platelets by 60% (P < .01). In addition, we treated human blood donors with 750 mg of oral aspirin, and evaluated the stimulatory effect of epinephrine-activated platelets on IL-8 secretion by EC. IL-8 synthesis after aspirin ingestion was inhibited by 90% (P < .01) as compared with the preaspirin stimulation. These observations show that activated platelets induce IL-8 secretion via membrane-associated IL-1 activity, and provide a novel relationship between coagulation and inflammation that could be relevant to several diseases.

Adenosine Diphosphate↗
PubMed1993

Granulocyte-endothelium initial adhesion. Analysis of transient binding events mediated by E-selectin in a laminar shear flow.

The adhesion of moving cells to receptor-bearing surfaces is a key step to many important biological processes. Attachment was subjected to extensive modeling. However, the numerical values of kinetic bonding parameters relevant to realistic models of cell adhesion remain poorly known. In this report, we describe the motion of human granulocytes to interleukin-1-activated endothelial cells in presence of a low hydrodynamic drag (a few piconewtons) estimated to be much weaker than a standard ligand-receptor bond. It was thus expected to visualize the formation and rupture of individual bonds. We observed multiple short-time cell arrests with a median duration of 2.43 s. Stop frequency, not duration, was significantly inhibited by anti-E-selectin antibodies. Binding efficiency exhibited an almost linear relationship with the inverse of cell velocity. The distribution of arrest duration was determined: results were consistent with the view that these arrests reflected the formation/dissociation of single ligand-receptor bonds with a spontaneous dissociation rate of 0.5 s-1. The rate of bond formation was on the order of 0.04 s-1 when cells were freely rolling (mean velocity: 19 microns/s) and it exhibited an approximately 10-fold increase after the formation of a first adhesion.

Cell Adhesion↗