[Immunoregulatory function of macrophages].
This review describes the role of macrophages in antigen processing and cell-cell interactions. The function of macrophages as secretory cells also is discussed.
Cell Communication↗
Biomedical subjects
M Janusz
Publications and source records attributed to M Janusz.
Effect of a proline-rich polypeptide (PRP) on the development of hemolytic anemia and survival of New Zealand black (NZB) mice.
PRP, administered intraperitoneally into NZB mice, twice a week, at doses 0.01-1 microgram per mouse, significantly lowered the incidence of positive Coombs' reaction and prolonged the mean age of the mice. The effect of PRP on survival of mice was better when the treatment with PRP started early (in mice showing first signs of the disease). The results suggest that PRP may induce, from a precursor pool of cells, suppressor cells controlling development of the disease. In addition, the data indicate that PRP may have a therapeutical value in treatment of autoimmune disorders, e.g. the juvenile arthritis.
Anemia, Hemolytic, Autoimmune↗
Shedding of the guinea pig peritoneal macrophage Fc gamma receptor. Effect on apparent association constant and on the number of IgG-binding sites on the cells.
During our studies on the structure and properties of guinea pig peritoneal macrophage Fc gamma receptor we observed that these cells spontaneously release an IgG-binding material into supernatant. Although the shedding was accompanied by a decrease in IgG-binding ability of macrophages, the number of IgG-binding sites/cell before and after shedding was similar. However, macrophages after the shedding interacted with IgG with a lower apparent association constant, Ka. Therefore, we assume that the decrease of IgG-binding ability of cells was an effect of decrease in value of Ka. Experiments with protein synthesis inhibitors showed that the shed receptor is replaced by "de novo" synthesized receptor molecules.
Animals↗
Differentiation of T cells into helper cells from immature precursors: identification of a target cell for a proline-rich polypeptide (PRP).
We demonstrated, with the aid of PRP, that precursors of helper T cells in the humoral immune response to SRBC belong to a minor thymocyte subset bearing the: Thy-1 +/-, H-2+, L3T4-, lyt 2-, CD3- phenotype. We showed, in addition, that PRP induced among the double negative (L3T4-, lyt 2-) thymocytes an appearance of differentiation antigens such as: L3T4, lyt 2, CD3 and T-cell receptor (alpha/beta). The data presented in this paper are in accordance with the present view on the process of T-cell maturation.
Animals↗
[Early reaction of rejection of esperal after implantation].
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Abdominal Muscles↗
A colostral protein that induces the growth and differentiation of resting B lymphocytes.
We describe the first protein of mammalian origin that induces the growth and differentiation of resting B lymphocytes. A proline-rich protein has been isolated from sheep colostrum. A purified proline-rich protein preparation (PRPP) induced resting mouse B cells into and supported their progression through the cell cycle at frequencies comparable with those seen for LPS. Differentiation of resting B cells to plaque formation was also supported as efficiently by PRPP as it was by LPS. However, PRPP was distinct from LPS in that it supported the growth and differentiation of resting B cells derived from either C3H/Tif or C3H/HeJ mice. Splenocytes from neonatal mice responded robustly to PRPP with the growth and differentiation of contained B cells to plaque formation. Unlike LPS, PRPP did not induce detectable Ig isotype switching.
Animals↗
Conformational modification of the PRP-hexapeptide by a direct covalent attachment of aromatic side chain groups.
PRP-hexapeptide possessing the azo-bridge between Tyr1 and Phe5 residues, called azo-PRP-hexapeptide: (formula; see text), was synthesized and tested for immunoregulatory activity. High biological activity of the synthesized azo-PRP-hexapeptide suggests that the biologically active conformation of PRP-hexapeptide must be such that both aromatic rings (Tyr and Phe) are apparently close to each other.
Adjuvants, Immunologic↗
Proline-rich polypeptide (PRP) from ovine colostrum. Bi-directional modulation of binding of peanut agglutinin, resistance to hydrocortisone, and helper activity in murine thymocytes.
A proline-rich polypeptide (PRP) isolated from ovine colostrum has a regulatory effect on the immune response. The present report demonstrates that the polypeptide can cause bi-directional modulation of surface markers and function of murine thymocytes. PRP is able to reduce binding of peanut agglutinin (PNA) to murine PNA+ thymocytes and to increase the binding of PNA to PNA- cells. This transition of binding ability can be reversed by a second treatment of cells with PRP. PRP is also able to transform cortisone-resistant thymocytes into cortisone-sensitive, and vice versa. Helper cells induced by PRP from murine glass-nonadherent thymocytes (PNA+) showed suppressor activity after the second treatment with PRP. The observed changes were occurring concomitantly, i.e. changes in binding of PNA were accompanied by changes in resistance to cortisone and in expression of helper or suppressor activity. Bi-directional effects of PRP on PNA-binding ability, sensitivity to hydrocortisone, and helper-suppressor function, makes this polypeptide unique among immuno-modulators known.
Animals↗
Interaction of membrane-bound Fc gamma receptors with the cytoskeletal matrix.
Binding of ligands to cell surface receptors may induce an interaction of the receptors with the cell cytoskeleton. This interaction may decrease the solubility of the receptors in nonionic detergents. We studied effect of binding of various 125I-labeled immunoglobulin ligands to Fc gamma receptors on guinea pig peritoneal macrophages and human placental syncytiotrophoblast plasma membranes on an interaction of these receptors with the cytoskeletal matrix. The receptor-cytoskeleton association was evaluated by measurement radioactivity of bound ligands in pellets and supernatants obtained after lysis of cells or membranes in a nonionic detergent NP-40. Binding of soluble immune complexes or crosslinking of IgG bound induces much stronger insolubilization of the receptors than binding of monomeric or aggregated IgG. It shows that the interaction of the receptors with the cytoskeletal matrix strongly depends on the degree of cross-linking of the Fc gamma receptors by ligands bound. The observed effects were IgG Fc region-specific. Isolated, purified putative Fc gamma receptors from guinea pig peritoneal macrophages and from human placental syncytiotrophoblast plasma membranes do not interact with free G or F actin. We also studied association of the guinea pig peritoneal macrophage Fc gamma receptor with the cytoskeleton, before and after shedding of macrophage membrane proteins. The results obtained showed that the macrophages have only one class of Fc gamma receptors interacting with the cytoskeletal matrix. Effect of a cytoskeleton-destabilizing buffer and DNAse I on release of the receptors from the cytoskeleton suggests that insolubilization of ligand-Fc gamma R complexes was caused, at least partially, by an interaction of the receptors with actin filaments in the cytoskeleton. The results presented in this paper suggest that the cytoskeleton might play a role in transmission of signals from Fc gamma receptors to the cells. They underline the role of immune complexes as physiological ligands for Fc receptors and correlate well with activation of cells via their Fc receptors (e.g. superoxide burst) observed by other authors after treatment of the cells with immune complexes, but not with monomeric or aggregated IgG.
Animals↗
Immunoregulatory properties of synthetic peptides, fragments of a proline-rich polypeptide (PRP) from ovine colostrum.
It has been previously found that a proline-rich polypeptide (PRP) isolated from ovine colostrum has a regulatory effect on the immune response. A nonapeptide fragment Val-Glu-Ser-Tyr-Val-Pro-Leu-Phe-Pro was isolated from the chymotryptic digest of PRP. The nonapeptide showed biological activity similar to PRP. The determined amino acid sequence was now confirmed by synthesis. Synthetic nonapeptide as well as its C-terminal hexapeptide, Tyr-Val-Pro-Leu-Phe-Pro, showed biological activity similar to PRP and the nonapeptide obtained from PRP.
Animals↗
Proliferative response of T lymphocytes to a proline-rich polypeptide (PRP): PRP mimics mitogenic activity of Il-1.
Mitogenic properties of a proline-rich polypeptide were investigated. The mitogenic action of PRP was compared with the mitogenic action of Il-1. PRP was not mitogenic for thymocytes at doses 0.01-50 micrograms/ml. PRP, at doses 0.1-50 micrograms/ml, augmented the proliferative response of thymocytes to Con A in a similar fashion as Il-1. At doses higher than 10 micrograms/ml, PRP induced proliferation of lymph node cells and splenocytes as well as T cells from the lymph nodes. It did not, however, cause significant proliferation of B cells from the lymph nodes, at the doses used. PRP did not induce proliferation of an antigen specific Lyt 1+ T cell clone. Il-1 behaved in a similar way as PRP in all the tests described. We consider a possibility that under physiological conditions, at a very early stage of postneonatal life, PRP may replace some functions of Il-1.
Animals↗
A mild method for the purification of guinea pig peritoneal macrophage Fc gamma receptors. Affinity chromatography and elution of the receptor with reducing agents.
A method for the purification of Fc gamma receptors from guinea pig peritoneal macrophages using mild conditions is described. The method is based on the observation that reduction and alkylation of IgG disulfide bonds partially or completely abrogate their binding to Fc gamma receptors. Cell lysates were directly applied to Sepharose-IgG or Sepharose-TNP-Ab(IgG) and the specifically bound Fc gamma receptor was eluted from adsorbents by incubation with reducing agents (2-mercaptoethanol or dithiothreitol). Alternatively, cell lysates were first treated with IgG and then applied to Protein A-Sepharose and the receptor was eluted with reducing agents. Yields of the purified Fc gamma receptor preparations and their activities were considerably higher than when the receptor was eluted from affinity chromatography gels with acetic acid or other acidic buffers or chaotropic agents. The best results were obtained when Fc gamma receptor-IgG complexes were applied to Protein A-Sepharose. No significant difference in the subunit structure was observed using SDS-PAGE when receptor preparations obtained by elution with reducing agents were compared with preparations obtained by elution with acidic buffers.
Animals↗
A proline-rich polypeptide (PRP) with immunoregulatory properties isolated from ovine colostrum. Murine thymocytes have on their surface a receptor specific for PRP.
A proline-rich polypeptide (PRP) was isolated from ovine colostrum. The polypeptide exhibits immunoregulatory properties. It induces maturation of murine thymocytes into functionally mature helper or suppressor T cells. To elucidate the mechanism of interaction of the polypeptide with thymocytes, effect of PRP immobilized on insoluble carriers on thymocytes was compared with the effect of soluble PRP. It was found that PRP covalently linked to cellulose discs or AffiGel 702 or adsorbed on polystyrene latex beads shows activity similar to activity of PRP in solution. A contact of PRP with the cell surface is satisfactory to induce maturation of thymocytes. PRP adsorbed on polystyrene latex beads forms rosettes with thymocytes. Formation of rosettes is specifically inhibited by soluble PRP. The results obtained suggest that murine thymocytes have on their surface a receptor specific for PRP.
Animals↗
Effect of proline-rich polypeptide on experimental autoimmune response to erythrocytes.
PRP administration in parallel with RRBC injections increased the AEAP in mice, as did adult thymectomy carried out six weeks before the RRBC injections. On the other hand, PRP administration to thymectomized mice during immunization with RRBC decreased the intensity of AEAP to the level observed in intact, RRBC immunized controls. The number of ARFC among non-B lymphocytes in peripheral blood was increased in mice immunized with RRBC compared to those in non-immunized animals. PRP administration during immunization with RRBC or adult thymectomy lowered their number below the values in non-immune animals and non-B ARFC number comparable to those in control, immunized animals was observed in thymectomized mice injected with PRP in parallel with RRBC. The values of ARFC among the NAL were higher than among the non-B lymphocytes but their shifts in the individual experimental groups were in the same direction as among the non-B lymphocytes. However, their shifts after thymectomy and/or PRP treatment were in opposition to those of the intensity of AEAP in the respective experimental groups.
Animals↗
Proline-rich polypeptide from ovine colostrum: its effect on skin permeability and on the immune response.
The effect of a proline-rich polypeptide from ovine colostrum on the humoral immune response in mice against sheep red blood cells (SRBC) was studied. It was shown that the polypeptide had a regulatory activity stimulating or suppressing the immune response. The proline-rich polypeptide also increased the permeability of skin vessels in guinea-pigs. Studies on the mechanism of the effect of the proline-rich polypeptide suggest that prostaglandins are involved in the activity of the polypeptide.
Animals↗
Differences in the purification effect of carcinoembryonic antigen (CEA) from the three different hepatic metastases of rectum carcinoma.
Carcinoembryonic actigen (CEA) was purified from three liver metastases of carcinoma recti by a conventional procedure involving perchloric acid extraction of tumor tissue and fractionation of the extract by gel filtrations on Sepharose 4B and Sephadex G-200. The preparations obtained showed a different degree of heterogeneity in SDS-polyacrylamide gel electrophoresis and crossed immunoelectrophoresis, and also a different antigenic activity. One of preparations obtained was a homogeneous CEA by all these criteria, and two others showed heterogeneity and lower antigenic activity. The most heterogeneous CEA preparation was further purified by the affinity chromatography on Concanavalin A-Sepharose 4B and by DEAE-Sephadex A-50 chromatography and the usefulness of these procedures for purification of CEA is compared.
Carcinoembryonic Antigen↗
[Rule of antibody structure: the primary structure of a human monoclonal IgA1-immunoglobulin (myeloma protein Tro), II. Cleavage of the monomer IgA-molecule and the reduced and alkylated H- and L-chains by cyanogen bromide (author's transl)].
The monomer of myeloma protein Tro as well as the reduced and alkylated H- and L-chains were cleaved by cyanogen bromide. All cyanogen-bromide fragments were isolated and characterized by amino acid analyses, end-group and molecular weight determinations. The 4 smaller fragments of the 5 H-chain fragments were split with trypsin. The peptides were isolated and their primary structure was determined.
Amino Acid Sequence↗
Physicochemical properties of a proline-rich polypeptide (PRP) from ovine colostrum.
Properties of a proline-rich polypeptide (PRP) accompanying ovine colostral IgG2 are described. PRP is soluble at 4 degrees C but reversibly precipitates by warming to room temperature. Maximal precipitation is observed at pH = 4.6, temp. 48 degrees C, and ionic strength higher than 0.6. There is a linear dependence of precipitation on concentration of PRP. Molecular weight of PRP is 38,000 daltons. It is not changed in the presence of 6 M guanidine hydrochloride, SH-compounds, and in the presence or absence of metal ions. PRP is built of one polypeptide chain. No difference in proteolysis of IgG2 by pepsin, papain and trypsin in the absence or presence of PRP was found.
Animals↗