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Biomedical subjects

F Tacchini-Cottier

Publications and source records attributed to F Tacchini-Cottier.

29 records · Page 2Linked to original sources
PubMed1995

Inactivation of E alpha and E beta expression in inbred and wild mice by multiple distinct mutations, some of which predate speciation within Mus species.

The H-2 MHC of mice encodes two functional class II heterodimeric proteins: A alpha A beta (A) and E alpha E beta (E). While failure to express the A protein has not been reported, a significant proportion of of H-2 haplotypes in both inbred and wild mice do not express E proteins. We and others have previously characterized the molecular basis for defective E expression in haplotypes from Mus domesticus (b, f, q, s, from inbred strains) and M. castaneus (w17, wild-derived) species, identifying six distinct defects in the genes for E alpha or E beta. In this report we have extended these studies to other E- haplotypes, including several from t-haplotype-bearing M. domesticus mice (w29, w57, w302) and one derived from the Asian species M. bactrianus (w301). Analyses at the protein, RNA and DNA levels were employed to identify the defects in the genes for Ea and Eb. At least one new defect was identified that prevents E beta expression in a t-associated H-2 haplotypes (w57), bringing the number of distinct mutations causing the E- phenotype to seven. Another t-associated haplotype, w302, was found to share the same E beta defect with mice of the inbred q haplotype and of the w17 haplotype from M. castaneus, while its Ea gene contains the deletion carried also by the inbred b and s haplotypes and by a number of wild haplotypes. The mutations in the Ea and Eb genes of the w301 haplotype from M. bactrianus were found to be identical to those of the inbred f haplotype. This indicates that the origin of the mutations in the Eb genes of the q, w17 and w302 haplotypes and in the Ea and Eb genes of the f and w301 haplotypes, predated speciation within Mus, thought to have occurred approximately 0.35-1 million years ago. Their maintenance in mouse populations suggests that in certain conditions the failure to express E alpha E beta proteins may be advantageous and selected for.

Amino Acid Sequence↗
PubMed1995

Administration of anti-TNF-alpha or anti-CD11a antibodies to normal adult mice decreases lung and bone collagen content: evidence for an effect on platelet consumption.

Administration of anti-tumor necrosis factor-alpha (anti-TNF-alpha) or anti-CD11a (LFA-1) antibodies to normal adult mice for about 10 days markedly decreased the hydroxyproline content in lung and femur. Similar observation was made using the recombinant soluble TNF receptor (rsTNFR) as tumor necrosis factor-alpha (TNF-alpha) antagonist. This decrease in collagen content was most likely due to a decrease of collagen synthesis, as evidenced by a decrease of the 3H-proline incorporation in lung and bone and by a decrease of collagen alpha 1 (I) mRNA levels in the lung RNA. The localization of labeled platelets in the lung of normal mice was decreased by anti-TNF-alpha but not by anti-CD11a antibodies. Thrombocytopenia increases the localization of labeled platelets in the lung, and, in this condition, both anti-TNF-alpha and anti-CD11a antibodies decreased pulmonary trapping. TNF-alpha mRNA was detected in the lung of normal adult mice, suggesting that this cytokine is released in the absence of inflammation. These results indicate that in vivo, endogenous TNF-alpha stimulates collagen synthesis, most likely by its influence on platelet trapping, which appears to involve the platelet CD11a since it is decreased by anti-CD11a antibody.

Animals↗
PubMed1995

Detection of a LFA-1-like epitope on the surface of erythrocytes infected with a strain of Plasmodium falciparum.

The adhesion of erythrocytes infected with Plasmodium falciparum (P. falciparum) is one of the major pathological features of severe malaria. Several potential receptors to endothelium for falciparum-infected erythrocyte on endothelium have been described. Recently, the malaria binding site on ICAM-1(CD54) has been mapped to a site distinct but overlapping with the LFA-1 (CD11a/CD18) site. We detected by flow cytometry, confocal laser microscopy and immunoprecipitation, a molecule expressed at the surface of erythrocytes infected with mature stages of the M96 strain of P. falciparum that was recognized by a monoclonal antibody (mAb) (TS1/22) directed against an LFA-1 epitope. However, this molecule was not recognized by mAbs directed against other epitopes of LFA-1 or against other integrins. Furthermore, the mAb TS1/22 partially inhibited cytoadherence of parasitized red blood cells to human-brain microvascular endothelial cells. The expression of a molecule sharing an epitope with human LFA-1 integrin on the parasitized erythrocyte surface could be involved in the sequestration of these cells and thus in the pathogenesis of severe disease.

Antigens, Protozoan↗
PubMed1994

Exposure of monocytes to heat shock does not increase class II expression but modulates antigen-dependent T cell responses.

Expression of heat shock (HS) proteins (HSP) increases after exposure to elevated temperatures or other types of injury, such as oxidative injury. Because of their function as 'molecular chaperones', HSP are suggested to participate in antigen processing and presentation. We have previously reported that HS modulates antigen presentation in a human EBV-transformed B cell line. Here we investigated the effects of HS on MHC class II expression and on antigen processing and presentation by human monocytes. Monocytes were isolated from peripheral blood of normal human volunteers, purified by adherence, then exposed to temperatures ranging from 37 to 45 degrees C for 20 min, allowed to recover for 2 h at 37 degrees C and used for immunofluorescence or as antigen presenting cells in autologous and heterologous lymphocyte proliferation assays. No increase in class II expression was detected as assessed by flow cytometry. Monocytes (3 x 10(4)) and lymphocytes (1 x 10(5)) were co-cultured for 5 days in the presence of several antigens [diphtheria toxoid, tetanus toxoid or purified peptide derivative (PPD)] and labeled with 1 microCi [3H]thymidine for 16 h. Pre-exposure to HS (44 degrees C) significantly (P < 0.001) increased T cell responses to diphtheria toxoid, whereas the effect on the responses to other antigens (tetanus toxoid or PPD) were not significant. HS did not increase heterologous T cell responses nor T cell proliferation induced by the non-processed superantigens such as staphylococcal enterotoxin B. The effect of HS was inhibited by actinomycin B and thus appeared dependent upon HSP synthesis. HSP-mediated increases in antigen processing may potentiate the ongoing immune response at inflammatory sites.

Antigen Presentation↗
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↗
PubMedDate not supplied

Some of the early events underlying Th2 cell maturation and susceptibility to Leishmania major infection in BALB/c mice.

The first experimental evidence for the development of polarized CD4+ Th1 and Th2 responses in vivo has been obtained using the murine model of infection with Leishmania major, an intracellular parasite of macrophages in their vertebrate host. Genetically determined resistance and susceptibility to infection with this parasite have been clearly demonstrated to result from the development of polarized Th1 and Th2 responses, respectively. Using this model system, the dominant role of cytokines in the induction of polarized CD4+ responses has been validated in vivo. The requisite role of IL-4 in mediating both Th2 differentiation and susceptibility to infection in BALB/c mice has directed interest towards the search for evidence of IL-4 production early after infection and identification of its cellular source. We have been able to demonstrate a burst of IL-4 production in susceptible BALB/c mice within the first day of infection with L. major and could establish that this rapidly produced IL-4 instructed Th2 lineage commitment of subsequently activated CD4+ T cells and stabilized this commitment by downregulating IL-12 Rbeta2 chain expression, resulting in susceptibility to infection. Strikingly, this early IL-4 response to infection resulted from the cognate recognition of a single epitope in a distinctive antigen, LACK, from this complex microorganism by a restricted population of CD4+ T cells that express Vbeta4-Valpha8 T cell receptors.

Animals↗
PubMedDate not supplied

Interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in pregnant C57BL/6 mice infected with L. major at different gestational periods.

BACKGROUND AND OBJECTIVE: To assess if gestational factors affect the resistance of C57BL/6 mice to L major infection, this study determined the levels of IL-4 and IFN-gamma in popliteal lymph node cells of pregnant C57BL/6 mice infected with L. major at 16 hours, 5 days-, 10 days- and 15 days- post plug by PCR, ELISA and BIOASSAY. DESIGN/SETTING: Experimental. RESULTS: Infected pregnant C57BL/6 mice developed larger cutaneous footpad lesions compared with non-pregnant C57BL/6 mice (that showed signs of resolution 7-10 weeks after infection). But, the lesions in infected pregnant C57BL/6 mice and infected non-pregnant C57BL/6 mice were not as large as in susceptible BALB/c mice. The mean litter weight was also reduced in pregnant infected C57BL/6 mice particularly in the groups infected at later stages of pregnancy (day 10- and day 15-post plug). The levels of both IL-4 and IFN-gamma increased with gestation in pregnant infected C57BL/6 mice compared with pregnant non-infected group, while only IL-4 was raised in pregnant infected mice compared with infected non pregnant mice. CONCLUSIONS: It may be concluded that increased IL-4 in pregnant infected C57BL/6 mice caused the transient susceptibility to L major infection while reduced litter weight was associated with increased IFN-gamma. These effects were pronounced in C57BI/6 mice infected with L major in late pregnancy.

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↗