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Biomedical subjects

C Vesin

Publications and source records attributed to C Vesin.

35 records · Page 2Linked to original sources
PubMed1994

Role of polymorphonuclear neutrophil leukocytes and their integrin CD11a (LFA-1) in the pathogenesis of severe murine malaria.

Infection of CBA mice with Plasmodium berghei ANKA results in severe malaria, which is characterized by mortality 6 to 10 days after infection and is associated with alterations of the brain microcirculation. These alterations consist of (i) intravascular sequestration of monocytes, (ii) an increase in vascular permeability as documented by Evans blue diffusion, and (iii) microhemorrhages. This syndrome may be due to an increase of production of tumor necrosis factor alpha which upregulates the endothelial expression of ICAM-1 and thus leads to adhesion of CD11a/CD18 (LFA-1)-bearing cells. During severe malaria, we found an important sequestration of the CD11a-bearing polymorphonuclear neutrophil leukocytes (PMN) in the lung but not in the brain. Treatment with a monoclonal antibody (MAb) against PMN, which induces profound neutropenia, prevented mortality and Evans blue diffusion in the brain and the lung, while it unexpectedly increased the occurrence of microhemorrhages. The anti-PMN MAb abolished PMN sequestration in the lung and also partially decreased monocyte sequestration in the brain and the lung. Treatment with an anti-CD11a MAb also prevented mortality, Evans blue diffusion, and PMN and monocyte sequestration. This study shows that PMN contribute to the mortality and the microvascular lesions resulting from severe malaria. This may be due to their CD11a-dependent sequestration in the lung and also to their indirect influence on vascular permeability and the sequestration of monocytes.

Animals↗
PubMed1994

Treatment by human recombinant soluble TNF receptor of pulmonary fibrosis induced by bleomycin or silica in mice.

Intratracheal instillation of bleomycin (0.08 U) or silica (2 mg) to mice leads, after 15 days, to a patchy pulmonary fibrosis associated with a significant increase of the lung hydroxyproline. Since tumour necrosis factor (TNF) seems to be an important mediator in pulmonary fibrosis, we wondered whether this fibrosis might be prevented by a new TNF-alpha antagonist. Infusion of a 55 kD human recombinant soluble TNF receptor rsTNFR-beta, at a rate of 20 micrograms.day-1, prevented the bleomycin/silica induced increase of lung hydroxyproline content, as measured 15 days after instillation. Infusion of rsTNFR-beta was also effective in the treatment of an established fibrosis, i.e. administered 25 or more days after instillation of bleomycin or silica, since it reduced lung collagen content. Recombinant soluble TNFR-beta had no significant influence on the number of cells, mostly macrophages, recovered by bronchoalveolar lavage. The examination of histological sections indicated that the rsTNFR-beta reduced the proportion of areas of damaged lung and, in silicosis, the formation of nodules with a rich collagen content. This study suggests that rsTNFR-beta might be useful in the therapy of pulmonary fibrosis.

Animals↗
PubMed1994

Pulmonary platelet trapping induced by bleomycin: correlation with fibrosis and involvement of the beta 2 integrins.

Platelet trapping was explored during the course of bleomycin induced pulmonary fibrosis by the injection of indium-111 labelled platelets and by light and electron microscopy (EM) of the alveolar capillaries. An i.v. injection of bleomycin markedly increased the localization of labelled platelets in the lung (but not in other organs) for about 3 weeks. On day 7 after bleomycin injection, a significant increase in the number of platelets in contact with the alveolar endothelium was seen with EM. Platelet trapping was strongly correlated (P < 0.005) with collagen deposition when examined in mouse strains genetically susceptible (CBA, C57BL/10, BL10 A.2R), or resistant (Balb/c, BL10.D2, BL10.A), to bleomycin induced fibrosis. In addition, several treatments known to decrease bleomycin induced collagen deposition and synthesis, namely administration of antibodies against CD11a, CD11b, TNF-alpha and IL-1ra, also decreased platelet trapping. As evaluated by EM, anti CD11a mAb significantly decreased the number of platelets in contact with the alveolar endothelium. This study indicates that bleomycin induced pulmonary fibrosis is strongly correlated with platelet trapping and that platelets probably interact, via their CD11a, with the CD54 born by the alveolar endothelium.

Animals↗
PubMed1993

Respective role of polymorphonuclear leukocytes and their integrins (CD-11/18) in the local or systemic toxicity of lipopolysaccharide.

The role of neutrophils (PMNs) and leukocyte integrins was investigated in two models of lipopolysaccharide (LPS)-induced toxicity: the systemic lethality assay in D-galactosamine-sensitized mice and the local reaction elicited by intradermal injection of LPS and tumor necrosis factor (TNF) at 24-h intervals. In the local reaction, depletion of PMNs with an anti-PMN monoclonal antibody (mAb) and mAbs against CD-11a (or LFA1) and CD-11b (or CR3) completely prevented the hemorrhagic necrosis. Evaluation of histological sections and myeloperoxidase levels suggested different mechanism of protection because PMNs were abundant in anti-CD-11- and absent in anti-PMN-treated mice. In the systemic assay, depletion of PMNs ensured 100% survival, whereas after administration of anti-CD-11a or b mAb, the percentages of survivors were 6 and 59%, respectively. One hour after LPS injection, the serum TNF-alpha level was higher in PMN-depleted mice than in controls. These studies provide evidence that neutrophils are essential for the expression of local or systemic LPS-induced injury, whereas the requirement for their leukocytic integrins is obvious only in the local reaction.

Animals↗
PubMed1993

Interleukin 1 receptor antagonist (IL-1ra) prevents or cures pulmonary fibrosis elicited in mice by bleomycin or silica.

We explored the role of interleukin 1 (IL-1) in two models of pulmonary fibrosis (PF), elicited in mice by the intra-tracheal instillation of bleomycin or silica. In both models, administration of IL-1 receptor antagonist (IL-1ra) by an osmotic minipump implanted i.p., at a rate of 0.5 microgram/h, completely prevented the collagen deposition, as evaluated by the lung hydroxyproline content on day 15 after instillation. IL-1ra had little or no influence on the number of cells recovered from the broncho-alveolar lavage. Study of histological sections suggests that IL-1ra globally decreased the proportion of damaged lung and particularly in silica the formation of nodules with a rich content in collagen fibrils. IL-1ra was also effective in reducing the lung hydroxyproline content when given on day 25 after instillation of bleomycin or silica, indicating that it may reverse established PF. This study indicates that IL-1ra might be useful for the treatment of incipient or established pulmonary fibrosis.

Animals↗
PubMed1993

Protective effect of natural TNF-binding protein on human TNF-induced toxicity in mice.

The in vivo protective effect of urinary TNF-binding protein (uTBP) on acute TNF-induced lesions and lethality was assessed in BALB/c mice. Two animal models, the local Shwartzman reaction and galactosamine (GaLN) induced TNF sensitization, were used. In the former, local cutaneous haemorrhagic necrosis induced by 10 micrograms of recombinant human TNF alpha (r-hTNF) was prevented with iv doses of uTPB as low as 1 microgram when administered concomitantly or 10 micrograms when injected intravenously 60 min before or 30 min after the lesion eliciting-dose of r-hTNF. In the latter model, injection of 1 microgram or r-hTNF caused the death of all mice within 36 h. Either 100 or 250 micrograms of uTBP given intravenously simultaneously with r-hTNF/GaLN totally prevented this mortality. In contrast to anti-human TNF monoclonal antibodies, these very same doses of uTBP significantly protected mice even when injected after the lethal r-hTNF dose. These data confirm in relevant in vivo pathological models the TNF inhibiting capacity of the natural soluble TNF receptor I.

Animals↗
PubMed1993

An effector role for platelets in systemic and local lipopolysaccharide-induced toxicity in mice, mediated by a CD11a- and CD54-dependent interaction with endothelium.

The role of platelets was investigated in two models of lipopolysaccharide (LPS)-induced toxicity in mice: the systemic reaction, provoked by intravenous LPS injection in D-galactosamine-sensitized recipients, which results in host death, and the local reaction, elicited in the skin by sequential injections of LPS and tumor necrosis factor alpha at 24-h intervals, which results in hemorrhagic necrosis. In both models, the depletion of platelets with a rabbit polyclonal or a mouse monoclonal antiplatelet immunoglobulin G afforded significant protection. In the local reaction, studies of the distribution of 111In-labelled platelets as well as optical and electron microscopy showed that platelets are localized in the dermal venules before hemorrhage occurs. Anti-CD11a (LFA-1) and anti-CD54 (ICAM-1) monoclonal antibodies prevented both platelet localization and hemorrhagic necrosis, and these determinants were detected on mouse platelets by immunofluorescence. The antiplatelet monoclonal antibody did not reduce the localization of polymorphonuclear leukocytes in the dermal venules, as shown by histological sections. Thus, in the local reaction, the stimulation with LPS and tumor necrosis factor alpha leads to a binding of platelets to the endothelium of venules by their beta 2 integrins, which seems necessary for the development of the hemorrhagic necrosis.

Animals↗
PubMed1993

Effective treatment of the pulmonary fibrosis elicited in mice by bleomycin or silica with anti-CD-11 antibodies.

We treated two types of experimental pulmonary fibrosis elicited in mice by the intratracheal instillation of bleomycin or silica with monoclonal antibodies (mAbs) specific for the leukocytic integrins CD-11a or CD-11b. This treatment completely prevented collagen deposition, as measured by lung hydroxyproline content on Day 15 after instillation. Furthermore, anti CD-11a mAb was also effective when given on Days 20 and 25 and the lung hydroxyproline content determined on Day 30 after instillation, i.e., in the treatment of an established pulmonary fibrosis. Histologic studies indicated that anti CD-11 mAbs attenuated the fibrosing alveolitis induced by silica or bleomycin and in addition markedly decreased the lymphoid infiltration and platelet microthrombi associated with both types of alveolitis. In contrast, these mAbs had little or no effect on the cellularity of the bronchoalveolar lavage, mainly composed of macrophages. In normal mice, anti CD-11 mAbs also decreased the number of interstitial lymphocytes and the lung collagen content. These observations may lead new to therapies for pulmonary fibrosis.

Animals↗
PubMed1992

Evolution of collagen arthritis in mice is arrested by treatment with anti-tumour necrosis factor (TNF) antibody or a recombinant soluble TNF receptor.

Immunization of DBA/1 mice with type II collagen within complete Freund's adjuvant leads to arthritis, lasting more than 3 months. Injection of anti-tumour necrosis factor (TNF) IgG, 2 and 3 weeks after immunization prevented the development of arthritis in the following months. This treatment had no effect when started 2 months after induction of the disease. A soluble form of the human recombinant TNF receptor type-beta (rsTNFR-beta), continuously infused at a rate of 20 micrograms/day during the second and third week after immunization, also had a long-term protective effect. Anti-TNF antibody had no effect upon the production of anti-type II collagen antibodies. These results indicate that TNF is critically involved in an early phase of this arthritis.

Animals↗
PubMed1991

Late administration of monoclonal antibody to leukocyte function-antigen 1 abrogates incipient murine cerebral malaria.

We analyzed the role of adhesion molecules in the pathogenesis of experimental cerebral malaria (ECM), since tumor necrosis factor (TNF) plays a major role in this condition and has been shown to up-regulate in vitro expression of cell adhesion molecules (CAM), particularly intercellular CAM-1 (ICAM-1). We found increased expression of ICAM-1 on brain endothelial cells from mice with ECM. Treatment with monoclonal antibodies (mAb) directed against leukocyte function-antigen 1 (LFA-1, the ligand of ICAM-1) on days 6, 8 and 10 almost totally prevented ECM, while decreasing blood TNF levels. To exclude the possibility that the effects of anti-LFA-1 mAb resulted from an even partial inhibition of TNF overproduction, mice with signs of imminent death (hypothermia and neurologic defects) were treated with the anti-LFA-1 mAb, with dramatically protective effect. In contrast, injection of anti-ICAM-1 mAb on day 6 caused rapid death, while it was innocuous in normal mice. An mAb directed against complement receptor type 3 (CR3) was ineffective, as were injections of soluble human ICAM-1. These results suggest that adhesion of LFA-1+ cells to endothelial cells, stimulated by TNF to express high levels of ICAM-1, is critical in the pathogenesis of ECM. Emergency therapy at interfering with cytoadherence could be considered in the treatment of cerebral malaria in man, in which high blood TNF levels are also observed.

Animals↗
PubMed1991

Prevention of human TNF-induced cutaneous Shwartzmann reaction and acute mortality in mice treated with anti-human TNF monoclonal antibodies.

We studied monoclonal antibodies (MoAbs) directed against human tumour necrosis factor (TNF) for their capacity to prevent toxic or lethal effects of TNF. Two experimental models involving recombinant human TNF (rhTNF) in mice were used: the Shwartzmann reaction, and the lethality after D-galactosamine sensitization. Two MoAbs were found to be protective in both models. These MoAbs prevented mortality when given 6 h, 4 h, or 15 min before rhTNF injection but were not effective if given after TNF. In addition, our results point out that in vitro binding and even neutralizing capacities of anti-hTNF MoAbs do not necessarily reflect their protective efficacy in vivo. Therefore, the models studied here might be useful to evaluate anti-h TNF MoAbs before clinical use.

Animals↗
PubMed1988

Immunopathology of thrombocytopenia in experimental malaria.

An early thrombocytopenia was observed in CBA mice during acute infection with Plasmodium berghei. This was associated with an increase in bone marrow megakaryocytes and a reduction of normal syngeneic 111Indium-labelled platelet life span. Malaria-induced thrombocytopenia was thus considered to be the result of increased peripheral platelet destruction rather than central hypoproduction. The occurrence of thrombocytopenia was modulated by T-cell depletion. Indeed, thymectomized, irradiated or anti-CD4 monoclonal antibody-treated mice failed to develop thrombocytopenia, although they were infected to the same extent. Conversely, a significant thrombocytopenia was observed in thymectomized mice reconstituted with CD4+ T cells. During the course of infection, a significant inverse correlation was found between platelet counts and platelet-associated IgG. Normal mice passively transferred with serum from syngeneic malaria-infected mice developed thrombocytopenia. The possibility to raise monoclonal anti-platelet antibodies from P. berghei-infected animals further suggested a role for an antibody-mediated platelet destruction during acute murine malaria infection. These results indicate that in murine malaria, thrombocytopenia is mediated by immune mechanisms and that CD4+ T cells might be significantly involved.

Acute Disease↗
PubMed1979

Seroepidemiology of cytomegalovirus infections during the first years of life in urban communities.

Using indirect haemagglutination assay, combined with a collection of blood samples on blotting cards, seroepidemiological surveys of cytomegalovirus infections during early infancy have been done in different populations (French and immigrant) in urban areas. The comparison of CMV antibody status of mothers and their children at 10 months and at 2 years of age enables possible factors of viral transmission to be defined. During the first year of life, seropositive mothers were the only source of infection and they remained the main source during the second year. Socioeconomic class and educational level are determinant factors in the incidence of viral transmission.

Child, Preschool↗
PubMedDate not supplied

Bombesin down modulates pulmonary fibrosis elicited in mice by bleomycin.

The role of bombesin was investigated in the course of the pulmonary inflammation and fibrosis (PF) elicited by the intratracheal (IT) or intravenous (i.v.) administration of bleomycin in mice. Bleomycin-induced alveolitis was associated with an accumulation of cells, presumably macrophages, containing bombesin, as evidenced by immunohistochemistry. Administration of bombesin by an osmotic minipump implanted IP, at a rate of 6 micrograms/h, decreased the lung hydroxyproline evident 15 days after IV or IT administration of bleomycin. In contrast, antibombesin monoclonal antibody 2A11 (mAb) increased the lung hydroxyproline content after IT administration of bleomycin. In addition, the mortality of bleomycin-injected mice was increased by the anti-bombesin mAb. Bombesin administration induced an increase, and anti-bombesin mAb induced a decrease, in the number of macrophages recovered from the bronchoalveolar lavage. Administration of bombesin did not change the mRNA levels of TNF-alpha, TGF-beta, and PDGF, as seen on Northern blots made with the lung RNA. Pulmonary platelet trapping, which was increased by a bleomycin injection, was decreased by an infusion of bombesin as demonstrated by the distribution of 111In-labeled platelets. This study indicates that bombesin act as an inhibitor of the development of pulmonary fibrosis, possibly by decreasing pulmonary platelet trapping.

Animals↗
PubMedDate not supplied

TNF-induced microvascular pathology: active role for platelets and importance of the LFA-1/ICAM-1 interaction.

Pathogenic mechanisms of brain microvascular injury were studied in an experimental model of cerebral malaria (CM). The lesion, leading to perivascular microhemorrhages, is due to cytokine overproduction, and is associated with the sequestration of macrophages and parasitized erythrocytes in cerebral venules. In this in vivo model, we demonstrate that platelets are critical effectors of the neurovascular injury. First, electron microscopy indicated that during CM platelets adhere to and probably damage brain endothelial cells. Second, radiolabelled platelet distribution studies indicated that platelets sequestered in the brain and lung vasculature during CM. Non-cerebral malaria was not associated with cerebral sequestration of platelets. Third, in vivo treatment with a mAb to LFA-1 (which is expressed on platelets) selectively abrogated the cerebral sequestration of platelets, and this correlated with prevention of CM. Fourth, malaria-infected animals rendered thrombocytopenic were significantly protected against CM, further indicating that platelets are central to the pathogenesis of CM. Thus, a CD11a-dependent interaction between platelets and endothelial cells appears pivotal to microvascular damage. These data suggest a novel mechanism of action for anti-LFA-1 mAb in vivo and illustrate an unexpected role of platelets, in addition to monocytes, in vascular pathology.

Animals↗