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Biomedical subjects

F Leyva-Cobian

Publications and source records attributed to F Leyva-Cobian.

10 recordsLinked to original sources
PubMed1993

Role of complement component C1q in phagocytosis of Listeria monocytogenes by murine macrophage-like cell lines.

Listeria monocytogenes is a facultative intracellular pathogen of a great variety of cells. Among them, macrophages constitute the major effector cells of listerial immunity during the course of an infection. Although the molecular bases of L. monocytogenes attachment and entry to phagocytes are not completely understood, it has been demonstrated that C3b significantly increases L. monocytogenes uptake by macrophages via complement receptor type 3. The first component of complement, C1q, is present in organic fluids at a relatively high concentration, and C1q receptor sites in macrophages are also abundant. In the present report, results of studies on the role of C1q in the internalization and infectivity of L. monocytogenes by macrophages are presented. L. monocytogenes uptake is enhanced by prior treatment of bacteria with normal sera. Heated serum or C1q-deficient serum abrogates this enhancement. Purified C1q specifically restored uptake. This effect was blocked by the addition of F(ab')2 anti-C1q antibody but not by an irrelevant matched antibody. Direct binding of C1q to L. monocytogenes was specific, saturable, and dose dependent with both fluorescent and radiolabeled C1q. N-Acetyl-D-alanyl-L-isoglutamine, diaminopimelic acid, and L-rhamnose caused a significant dose-dependent inhibition of C1q binding to bacteria, suggesting that these molecules, at least, are involved in the attachment of C1q to L. monocytogenes cell wall. When C1q binding structures on macrophage-like cells were blocked with saturating concentrations of C1q, the uptake of C1q-opsonized bacteria was less than in untreated cells. These experiments demonstrate that, in addition to other reported mechanisms, L. monocytogenes binds C1q, which mediates enhanced uptake by macrophages through C1q binding structures.

Animals↗
PubMed1992

Eosinophil as antigen-presenting cell: activation of T cell clones and T cell hybridoma by eosinophils after antigen processing.

We have studied the role of murine eosinophils as antigen-presenting cells (APC). Eosinophils have several characteristics that support the hypothesis of its function as potential APC: they have phagocytic capacity, express adhesion molecules and major histocompatibility complex (MHC) class II antigens and can produce and release interleukin-1 (IL-1). We have obtained several T cell clones specific for Mesocestoides corti antigens and used T cell hybridoma specific for ovalbumin (OVA) to test this hypothesis. Granulocyte-macrophage colony-stimulating factor-activated pure eosinophils (99.9%), express class II antigens and are able to present M. corti antigens to specific T cell clones or OVA to T cell hybridoma 3DO 11.10, inducing the proliferation of T cell clones and IL-2 release by the T cell hybridoma. Proliferation of T cells clones is dependent on the number of eosinophils used as APC. We have compared the efficiency of the same number of macrophages and eosinophils as APC, and have found that macrophages are more efficient than eosinophils. Lysosomotropic agents, such as chloroquine and ammonium chloride, that inhibit antigen processing, impaired eosinophil presentation. This presentation is restricted by MHC class II and inhibited by anti-I-Ad monoclonal antibody. The present study provides clear evidence of APC function for eosinophils. Our investigation points to a new role for eosinophils in the immune response.

Ammonium Chloride↗
PubMed1989

Serum levels of protein HC and its IgA complex in malignant melanoma.

Protein HC is a low molecular weight glycoprotein that is present as free form and in complex with IgA (HC-IgA) in human body fluids. In the present report, a combined competitive and sandwich enzyme-linked immunsorbent assay (ELISA) was used to measure the levels of protein HC and its IgA complex independently in the sera of patients with malignant melanoma. The concentration of these proteins correlated with IgA levels and clinical staging. The main findings can be summarized as follows: (1) protein HC and protein HC-IgA complex levels presented the most significant elevation in melanoma stages IVA and IVB; (2) a significant positive correlation was found between protein HC and protein HC-IgA complex values and the clinical stage of the tumor; (3) protein HC-IgA complex and IgA concentrations are parameters with positive correlation both in normal controls and in patients with melanoma; (4) in normal sera, the levels of protein HC and protein HC-IgA complex are not correlated, however, they are negatively correlated in melanoma.

Adult↗
PubMed1988

Intracellular interference with antigen presentation.

Murine peritoneal macrophages were cultured with heat-killed Listeria monocytogenes organisms and then with the protein hen egg white lysozyme. Hen egg lysozyme is well known to need intracellular processing for presentation to T cells. The presentation to T cells of lysozyme was affected despite no reduction in the amount taken up or catabolized by the macrophage. This interference with Ag presentation was not found if the macrophages were cultured with lysozyme before the Listeria pulse. The interference with Ag presentation induced by Listeria was found for a second Ag (conalbumin). Uptake of Listeria did not affect the presentation of the lysozyme peptide 46-61, indicating that MHC class II molecules were available at the macrophage surface. Other materials that are retained in the macrophages affected presentation of lysozyme but not of the processed peptide. These included SRBC, dextran, sucrose, cellobiose, polyvinyl pyrrolidone, sodium dextran sulfate, Ficoll, and polyethylene glycol. Except for SRBC, which were not tested, the remaining molecules did not interfere with presentation of 46-61 by formaldehyde-fixed macrophages, an indication that they did not affect the peptide interaction with class II molecules. Finally, uptake of latex beads did not affect presentation of lysozyme. We conclude that retention in the macrophage of a variety of soluble or particulate molecules can interfere with the intracellular events that result in the creation of an immunogenic determinant. This interference is independent of the catabolism of the Ag or of the availability of class II molecules to bind peptides.

Animals↗
PubMed1988

Identification of the protein HC receptor.

In the present study, we demonstrate for the first time the presence of a specific receptor for protein HC on the surface of human cells using the human histiocytic lymphoma cell line U937. Cells treated for 4 days with the maturation inducer phorbol 12-myristate 13-acetate, were found to increase both the number of cells binding protein HC (76% higher than for untreated cells) and the expression of protein HC receptors. Protein HC bound to these cells in a specific and saturable manner. Scatchard analysis at 4 degrees C, using radioiodinated protein HC, indicated a single class of low-affinity receptor (Ka = 2-5 x 10(7) M-1) and 20,000-30,000 receptors per cell. Monoclonal antibodies against protein HC abrogated specific binding of this protein to U937. In contrast, monoclonal antibodies that did not react with protein HC (anti-LFA-1 alpha, anti-MO1 alpha) were without effect on the binding reaction.

Alpha-Globulins↗
PubMed1988

Mechanisms of antigen processing.

Using MAb and monovalent Fab probes and saponin permeabilization we have demonstrated that PEC and TA3 B lymphoma-hybridoma cells contain a significant intracellular pool of Ia. At least in TA3 cells, this intracellular pool was independent of protein synthesis. In PEC, adherence caused redistribution of Ia with disappearance of the intracellular pool. Endocytosis of Ia occurred in both TA3 and PEC, and internalized Ia reached a plateau level corresponding in size to the total intracellular Ia pool revealed by saponin treatment. These results suggest that intracellular Ia is largely in a recycling pool derived from the plasma membrane by endocytosis. Subcellular fractionation studies suggest that Ia processing occurs in endosomes similar to those involved in transferrin processing. Antigen processing by TA3 cells was found to be unaffected by cycloheximide. In contrast, antigen processing by adherent PEC was markedly inhibited by cycloheximide, despite the fact that they maintained surface Ia and were still capable of presenting antigen peptides. This suggests that an important intracellular Ia processing step or antigen processing step was blocked in these cells. Adherent PEC may contain less recycling Ia, making protein synthesis the major source for intracellular Ia and the availability of intracellular Ia sensitive to cycloheximide. Alternatively, the inhibition of antigen processing by cycloheximide in PEC may reflect depletion of enzymes or other factors involved in antigen processing. Proteins and polysaccharides may interfere with the events that result in the formation of an immunogenic Ia-peptide complex. We had previously documented that peptides compete for the binding site of Ia molecules. We discussed here a second form of interference by polysaccharides and microbial products. These materials did not compete or interfere with the binding and presentation of processed peptides by Ia. Rather, their presence inside the macrophage inhibited MHC-dependent presentation of immunogenic proteins by inhibiting intracellular steps in antigen processing. This intracellular interference with antigen presentation can be of major importance in the presentation of complex mixtures of protein and carbohydrates.

Antigen-Presenting Cells↗
PubMed1984

Expression of Ia like (HLA-DR) antigens on human alveolar macrophages.

The distribution of Ia like (HLA-DR) antigens on human alveolar macrophages (HAM phi) has been investigated by indirect immunofluorescence staining of viable macrophages with a panel of monoclonal antibodies (MoAb) to common determinants of these antigens. HAM phi were characterized by non-specific esterase stain, plastic adherence, phagocytosis and IgG-Fc receptor expression. Ia like antigens were expressed in approximately 45-80% of HAM phi, being localized as patchy and lineal fluorescence along the membrane. Ia like expression was higher in macrophages from non-smoker subjects (P less than 0.025). No difference in Ia like antigen expression was found between adherent and non-adherent HAM phi subsets. Ia like positive HAM phi from both smoker and non-smoker subjects consisted of a large subpopulation of phagocytic cells (60-70%) and a smaller non-phagocytic subpopulation (20-25%). These subpopulations were also present in the Ia like negative HAM phi. The percentage of Ia like positive macrophages showed variable results depending on the MoAb used, suggesting that not all anti-Ia like antibodies recognize the same antigenic determinants. Moreover, lack of staining of one macrophage subset occurred with all MoAb tested, over a large range of concentrations.

Adolescent↗
PubMed1981

Evolution and characterization of renal immune complexes deposition in mice bearing a syngeneic tumor.

Immune complex deposition along the glomerular basement membrane (GBM) and in the mesangium in C57BL/6 mice bearing a transplantable syngeneic B16 melanoma is described. By immunofluorescence studies, IgG, IgM and C3 were found deposited along the GBM and the mesangium. Electron microscopy showed electron-dense deposits localized in GBM and mesangial matrix. The intensity of the immune complexes deposited in the glomeruli was correlated with progression of tumor size. In order to study the evolution of deposits, a monitoring protocol was designed. One group consisted of mice bearing B16 melanoma. They showed decreased immune complex deposition after tumor removal. Control mice inoculated with saline did not present immune complex deposition. Sham-operated mice bearing B16 melanoma showed progressive renal deposition of immune complexes. Immune complexes were made up of tumor antigen and antimelanoma antibodies and were partial characterized by elution, immunofluorescence and immunodiffusion procedures. Antimelanoma antibodies eluted from kidneys of tumor-bearing mice were of IgG class and reacted with a soluble product extracted from B16 melanoma cells.

Animals↗
PubMed1981

Familial C1q deficiency in 3 siblings with glomerulonephritis and Rothmund-Thomson syndrome.

Complete absence of C1q was demonstrated in the sera of 3 siblings in association with renal and cutaneous lesions. The serologic findings were consistent with an autoimmune disorder. Hematuria was the renal symptom present in all 3 patients; proteinuria was also present in 1. Renal biopsies showed mesangial proliferative glomerulonephritis with diffuse glomerular deposits of IgM and C3 in all cases. Clinical cutaneous manifestations and the histological picture were those of the Rothmund-Thompson syndrome. Three combined diseases, characterized by renal and cutaneous affection and serologic abnormalities, are presented in this paper.

Basement Membrane↗