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S Zolla-Pazner

Publications and source records attributed to S Zolla-Pazner.

150 records · Page 9Linked to original sources

A disposable diffusion chamber system used to study immunoregulation by soluble factors.

A disposable two-chamber culture system is described which is useful for studying various soluble factors which regulate the immune response. This method requires small numbers of cells and less than 2 ml of medium per culture. The vessel is compact, relatively inexpensive and all component parts are readily available from commercial suppliers. This culture system circumvents the major problems associated with dual chamber methods previously developed for the study of immunoregulatory molecules affecting antibody production.

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Markers of macrophage heterogeneity. I. Studies of macrophages from various organs of normal mice.

A unique subpopulation of macrophages (M phi) was identified among the spleen and bone marrow M phi of normal mice. After 24 h of culture, approximately 2.5% of the adherent cells cluster into "foci" of 10-30 cells. On the basis of their phagocytic and morphologic characteristics, these focus-forming M phi (FF-M phi) appeared to be highly activated. Uncoated sheep erythrocytes (E) were ingested by FF-m phi indicating that opsonization was not a prerequisite for phagocytosis. However, IgM-coated E (EIgM) were more readily phagocytosed by FF-M phi than were E suggesting that IgM is recognized as an effective opsonin by these cells. EIgM and E coated with IgM and complement (C) (EIgMC) were ingested by approximately the same percentage of FF-M phi; thus, if these cells possess complement receptors in addition to structures which bind EIgM, the C receptors do not enhance the ability of FF-M phi to ingest opsonized particles. The non-focus-forming M phi, e.g. individual M phi (I-M phi), in the spleen and bone marrow can, themselves, be divided into various subpopulations distinguished by their ability to bind and ingest E, EIgM ana EIgMC. These may represent various subpopulations of M phi or M phi at various stages of activation or differentiation. While spleen and bone marrow M phi contained FF-M phi and I-M phi which vary in their ability to ingest E, EIgM and EIgMC, theM phi of the peritoneum and blood of normal mice were far more homogeneous. Peritoneal and blood M phi did not form foci, ad did not ingest E or EIgM in significant amounts although a small percentage were able to ingest EIgMC. These data suggest that the population of M phi in the spleen and bone marrow are far more heterogenous than those found in the peritoneum or blood and that binding and phagocytosis of various coated and uncoated erythrocytes can be studied to elucidate this heterogeneity.

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Humoral mediator of antigenic competition demonstrated in vivo.

To determine if a soluble mediator of antigenic competition could be demonstrated in vivo, various groups of mice received implants of intraperitoneal Millipore diffusion chambers containing normal spleen cells and sheep erythrocytes (SRC). Priming and boosting the chamber hosts so that a vigorous secondary immune response to horse erythrocytes (HoRC) coincided with chamber implantation resulted in the suppression of the anti-SRC response of the chamber-enclosed cells. Similarly, passive immunization of the chamber hosts with SRC-absorbed anti-HoRC hyperimmune serum suppressed the response of the chamber-enclosed cells to SRC. Thus, serum from hyperimmune mice contains a humoral suppressor substance which mediates antigenic competition.

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Suppression of the humoral immune response by plasmacytomas: mediation by adherent mononuclear cells.

Mice bearing plasmacytomas have a severely impaired ability to mount a primary immune response; T cells from these mice, however, appear by both in vivo and in vitro criteria to function normally. This unusual pattern of immunodeficiency appears to be mediated by a regulatory cell found in the spleens and peritoneal cavities but not in the lymph nodes or thymuses of mice bearing plasmacytomas. The number of cells with suppressor activity in the spleens of plasmacytoma-bearing mice is directly proportional to the size of the subcutaneous tumor borne by the host. These cells are capable of suppressing antibody production in in vitro cultures of normal spleen cells but have no demonstrable effect on the ability of normal spleen cells to proliferate in vitro in response to phytohemagglutinin or 8-Br-guanosine-3', 5'-monophosphate (T and B cell mitogens, respectively). Characterization of the suppressor cell population on the basis of its cell surface properties, its radioresistance, its morphology, and its ability to adhere to various solid matrices suggest that these cells are adherent mononuclear cells. These data support the concept that plasma cell tumors indirectly induce an impairment in the humoral immune response of their hosts by stimulating the expression of regulatory functions in a population of splenic and peritoneal macrophages.

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Cellular specificity of plasmacytoma-induced immunosuppression.

The pattern of immunodeficiency in plasmacytoma-bearing mice appears to be unique. Mice bearing these tumors exhibit a severe impairment in their ability to mount a primary immune response to thymus-dependent and -independent antigens. However, cell-mediated immune functions in these mice apparently remain intact. Thus, when T cell activity of lymph node cells from plasmacytoma-bearing mice was tested in vivo by sensitization with dinitrofluorobenzene and in vitro by responsiveness to phytohemmagglutinin, allogeneic cells, and dinitrobenzene sulfonate, cell-mediated immunity was found to be normal.

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