Biomedical subjects

H H Fudenberg

Publications and source records attributed to H H Fudenberg.

At least 91 records · Page 5Linked to original sources

PubMed1983

Immune elimination of aging platelets by autologous monocytes: role of membrane-specific autoantibody.

Membrane-bound IgG was found only on old populations of platelets from normal individuals. This IgG could be dissociated from senescent cells by repeatedly heating the cells. Heat-eluted IgG (He-IgG) prepared from senescent red blood cells was capable of binding to either heat-treated old platelets or Vibrio cholerae neuraminidase (VCN)-treated young platelets, suggesting expression of a common age-dependent antigen on the senescent red blood cells and old platelets. We analyzed the role of membrane-bound IgG in the immune elimination of aging platelets by direct phagocytosis of different platelet subpopulations by autologous monocytes in vitro. While removal of He-IgG from old platelets inhibited their phagocytosis, preincubation of either heat-treated old or VCN-treated young platelets promoted phagocytosis of these cells by autologous monocytes. The phagocytosis of senescent cells required intact IgG on these cells. Either removal of Fc fragments from He-IgG or treatment of autologous monocytes with Fc fragments prior to the phagocytosis assay resulted in a marked reduction of phagocytosis (greater than 75%). We conclude that Fc receptors on the monocytes and the presence of membrane-specific IgG are crucial elements for immune elimination of senescent platelets.

Antigens, Surface↗

PubMed1983

Cultivation of human osteosarcoma cell lines in serum-free hormone supplemented medium.

Two human osteosarcoma cell lines (TE-85, LM-1) were adapted to grow in serum-free hydrocortisone supplemented medium. Human osteosarcoma associated antigens were detected both on the cell membrane as well as in the concentrated culture medium. TE-85 cells produced bone specific alkaline phosphatase and LM-1 cells produced both bone specific and placental-like alkaline phosphatases when cultured in this medium. Successful proliferation of human osteosarcoma cell lines in serum-free medium is valuable in human osteosarcoma research.

Alkaline Phosphatase↗

PubMed1983

Immune elimination of autologous senescent erythrocytes by Kupffer cells in vivo.

It has been shown previously that autologous monocytes recognize and phagocytose aging self-erythrocytes in vitro. The recognition requires the presence of an autoantibody present in all normal serum. Herein a similar mechanism of recognition and immune elimination of senescent erythrocytes in vivo is reported. When autologous rabbit red blood cells (RBCs), aged either in vivo or neuraminidase-treated young, were reinjected into the animal, most of the old RBCs were trapped in the liver while the majority of the young cells lodged in the spleen. Following reinjection of aging RBCs, the activity of microsomal heme oxygenase enzyme of the liver tissue increased greater than fourfold, suggesting erythrophagocytosis activity of Kupffer cells.

Animals↗

PubMed1983

Phagocytosis of senescent erythrocytes by autologous monocytes: requirement of membrane-specific autologous IgG for immune elimination of aging red blood cells.

The role of membrane-bound IgG present on the membrane of senescent erythrocytes in immune eliminations of aging red cells was investigated. Phagocytosis of populations of red blood cells (RBC) of different ages by autologous monocytes was assessed both by direct phagocytosis and by induction of microsomal heme oxygenase. Removal of IgG from older RBCs inhibited their phagocytosis; in contrast, preincubation of neuraminidase-treated young or in vitro aged RBCs with IgG eluted from old cells led to phagocytosis of RBCs treated by autologous monocytes. It was also found that the Fc portion of membrane-bound IgG is essential for the elimination of senescent cells; less than 15% of old heat-inactivated RBCs coated with F(ab)2 fragment of membrane-bound IgG were phagocytosed. In contrast, more than 50% of old heat-inactivated RBCs coated with heat-eluted IgG were phagocytosed by autologous monocytes. A possible mechanism of elimination of aged cells is discussed.

Adult↗

PubMed1983

Mechanisms for the removal of senescent human erythrocytes from circulation: specificity of the membrane-bound immunoglobulin G.

Direct antiglobulin (Coombs') tests of erythrocyte (RBC) subpopulations confirmed the presence of membrane-bound immunoglobulin G (IgG) on old (density greater than 1.110) human RBCs but not on the young (density less than 1.110) RBCs. After thermal elution of the bound IgG, this Coombs' reaction was negative, but incubation of thermally eluted IgG (He-IgG) with heat-treated RBCs induced a positive antiglobulin test. A positive direct antiglobulin reaction was also obtained after incubation of heat-treated RBCs with anti-T antibody. Similar results were obtained when young RBCs treated with Vibrio cholerae neuraminidase (VCN) were incubated with anti-T or with IgG eluted by heat from old RBCs. Nevertheless, pre-absorption of heat-eluted IgG with T and/or Tn antigen, did not prevent it from binding to either heat-treated old or VCN-treated young RBCs as assessed by the antiglobulin consumption assay. Pre-treatment of either VCN-treated young or heat-treated old RBCs with anti-T and/or anti-Tn antibodies had no significant effect on the binding of radiolabeled He-IgG (eluted from old RBCs). The results indicate that even though desialylation of the erythrocyte membrane is required for binding of both anti-T-Tn and He-IgG, the specificity and consequently the RBC binding sites for He-IgG and anti-T seem to be different.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1983

Radioimmunoassay for immunoglobulin G autoantibody on the surface of mouse erythrocytes.

A radioimmunoassay (RIA) for the determination of autoantibody on the surface of erythrocytes from New Zealand Black (NZB) mice is described. This method was adapted to hemagglutination plates in order to facilitate the separation of bound and unbound 125I-labeled rabbit anti-mouse immunoglobulin G with an automated cell harvester. Intra- and interday precision, over the useful quantitative range of the standard curve, was 3.9 and 12.9%, respectively. The RIA was five to ten times more sensitive than the direct antiglobulin test which, unlike the RIA, provided little quantitative information on a group of 20 experimental NZB mice. This is publication number 562 from the Department of Basic and Clinical Immunology and Microbiology, Medical University of South Carolina.

Animals↗

PubMed1983

Potentiation of factor H by heparin: a rate-limiting mechanism for inhibition of the alternative complement pathway.

The mechanism by which heparin inhibits the alternative complement pathway (ACP) by a fluid-phase activator, CoVF, has been studied. Results presented here indicate that heparin's major (rate-limiting) effect on the fluid-phase activation of the ACP was to potentiate Factor H activity. Such an effect results in a very efficient inhibition of C3b and C3bBb function and restriction of subsequent complement activation and hemolytic activity. Evidence was obtained to indicate that soluble heparin H shifted anodally. Assuming that the rate-limiting inhibitory effect of heparin is to potentiate Factor H, then C3-converting complexes such as CoVF-Bb, which do not require C3b for activity, should not be effected by heparin. Indeed, the inhibitory effect of heparin on C3 conversion in EGTA-Mg2+ serum-CoVF mixtures was lost with a prolonged incubation time (i.e. 60-90 min at 37 C). This finding indicated that with time ACP-mediated cleavage of C3 was able to bypass the heparin-mediated inhibitory step. From these studies it is suggested that heparin restricts the C3-converting activity due to soluble C3bBb complexes but not the C3 conversion due to CoVF-Bb complexes. Heparin-mediated restriction of the ACP activation by CoVF was used to calculate the relative percentages of C3 conversion due to C3bBb or CoVF-Bb complexes. In carefully controlled experiments, heparin could not prevent the spontaneous conversion of C3 which occurs upon removing functional Factor H from the sera. Addition of isolated Factor H restored heparin's inhibitory effect on the ACP. Kinetic studies of heparin's inhibition of ACP-mediated lysis of rabbit erythrocytes indicated that heparin's inhibitor functions did not occur until after the addition of an ACP activator. Each of these findings is consistent with the postulate that the major (rate-limiting) effect of heparin on the ACP is to potentiate the function of Factor H on activated C3b.

Complement Activation↗

PubMed1983

Cytotoxic antibodies to lymphocytes: relationship to sperm immunity.

Sperm and T lymphocytes share antigens, and sera from infertile subjects with sperm immunity have agglutinating antibodies to T lymphocytes. In the present study, cytotoxic antibody titers to sperm (C-Sp) and lymphocytes (C-Ly) were measured in sera, seminal plasma, cervical mucus and vaginal secretions of 52 infertile couples. The samples were divided into C-Sp negative and C-Sp positive groups. C-Ly titers against control T lymphocytes were significantly elevated in C-Sp positive sera of 35 males (P less than 0.005) and 27 females (P less than 0.05) as compared with C-Sp negative sera. C-Ly titers against autologous or partner T lymphocytes were similarly elevated in the sera of both groups. Titers of C-Ly in C-Sp positive secretions (seminal plasma, cervical mucus and vaginal secretions) against autologous and partner, as well as control, T lymphocytes were significantly elevated. In addition, elevated titers of C-Ly to autologous, partner and control B lymphocytes were observed in sera, cervical mucus and vaginal secretions from females with sperm immunity. The infertile males, however, did not have significant B lymphocyte immunity. Immunofluorescence assays revealed a significantly higher incidence of sperm and T lymphocyte antibodies (primarily IgG) in the C-Sp positive than in the C-Sp negative group. Titration of 100 sera from infertile subjects (50 couples) against a panel of lymphocytes of known HLA specificities failed to reveal a pattern of activity against HLA antigens of the A, B and C loci. Absorption of immune sera with sperm or lymphocytes reduced C-Sp and C-Ly titers significantly (P less than 0.001). These results suggest that infertile subjects with sperm immunity produce antibodies to cross-reactive antigens present on sperm and T lymphocytes.

Animals↗

PubMed1983

An in vitro study on the effects of isoprinosine on immune responses in cancer patients.

The in vitro effects of ISO on the immune responses of cancer patients were investigated. Forty seven patients with primary tumors (26 lung carcinoma, 14 breast adenocarcinoma, 7 melanoma) were studied. Concanavalin A (ConA)-induced lymphocyte proliferation, natural killer cell (NK) activity, and monocyte chemotaxis were measured. In 40 of the 47 patients (85%), ConA-induced lymphocyte proliferation was depressed; NK activity was depressed in 32 (68%), and monocyte chemotaxis was found to be depressed in 36 (77%). For in vitro studies, an optimum concentration of ISO (100 micrograms/ml per 10(6) cells) was used to treat peripheral blood mononuclear cells. In the presence of ISO, all three parameters were restored to normal or near normal levels in those that were depressed. Under these preincubation conditions in vitro treatment of mononuclear cells from the peripheral blood of normal individuals with ISO had no effect on their activities in the three assays. Similar effects on these three immune parameters were observed when 24 h supernatants obtained from patients' mononuclear cells pretreated with ISO were employed in these assays.

Adjuvants, Immunologic↗

PubMed1983

Gm allotypes in blacks with systemic lupus erythematosus.

Serum samples were collected from 328 healthy American Blacks and from 61 American Blacks with systemic lupus erythematosus (SLE). Sera were typed for the Gm1,2,3,5,6,13,17, and 21 allotypes as well as for the Km(1) allotype. The frequency of Gm phenotype 1,17;5,6,13 was significantly increased in the SLE patients (p = 0.0001, RR = 3.19, EF = 0.29). Our data suggest the existence of at least two immunoglobulin allotype associated genes that somehow interact to increase susceptibility to SLE in Blacks. To our knowledge, this is the first report of an association of Gm and SLE in Blacks.

Black People↗

PubMed1983

Is schizophrenia an immunologic receptor disorder?

A model is proposed for an autoimmune etiology for schizophrenia. We propose that schizophrenia is a syndrome (not a disease). We suggest that autoantibodies (and/or cell-mediated immunity) directed against autologous neurotransmitter receptors are responsible for the ebb and flow of psychotic symptomatology. The hypothesis is predicated on autoimmune models in other known receptor diseases as well as on the newly emerging recognition that general immune dysfunction exists in certain schizophreniform psychoses.

Antibody Formation↗

PubMed1983

In vitro humoral immune response of human peripheral blood lymphocytes to tetanus toxoid sepharose 4B.

The in vitro immune response of unfractionated human peripheral blood lymphocytes (PBL) from immune donors who had not been re-immunized with tetanus toxoid (TT) prior to donation was investigated. In this study we were able to stimulate PBL with tetanus toxoid coupled to Sepharose 4B (STT) for production of anti-tetanus toxoid antibody (Ab). Soluble tetanus toxoid or STT alone did not stimulate production of specific Ab. Pokeweed mitogen (PWM) and STT were required for optimal production of IgG and IgM antibodies specific to tetanus toxoid. Specific Ab responses were reduced in low and high concentrations of STT. Depletion of monocytes had no effect on either total IgG or specific IgG synthesis, but decreased the synthesis of both total and specific IgM. Depletion of E-rosette-forming cells decreased the production of specific Ab, suggesting T-dependency of the immune response to STT. Simultaneous production of total immunoglobulin and specific Ab by Sepharose 4B was negligible in the absence of PWM. In the presence of PWM, total immunoglobulin production was optimal, and specific anti-TT Ab production was undetectable. The specificity of the anti-TT Ab was studied by absorption of the culture supernates with an STT column which removed all measurable specific Ab.

Antibody Formation↗

PubMed1983

Activation of macrophages by in vitro allostimulated T cells.

Murine peritoneal macrophages, parabiotically co-cultured with combinations of in vitro H-2 sensitized thymus-derived lymphocytes obtained from drug-pretreated mice, possessed an increased cytotoxicity against alloantibody-coated target cells. This heightened activity appeared to be accentuated by and dependent on T-cell synergy. After 5 days of in vitro allosensitization at 37 degrees C, cortisone-resistant thymocytes allosensitized in combination with cyclophosphamide-pretreated splenic T cells released molecules that produced strong antibody-dependent macrophage-mediated cytotoxicity (ADCC). This enhanced ADCC correlated with increased macrophage rosetting with IgG-sensitized erythrocytes. These heightened activities resulted from soluble mediators released by the activated T cells which diffused across a 0.22-microns Millipore filter and were not dependent on lymphocyte-macrophage contact. Evidence that these molecules originated from the highly enriched T-cell populations and were not synthesized de novo by macrophages was supported by results of pretreatment with protein and RNA synthesis inhibitors. Evidence that soluble Fc receptors released from the alloactivated T cells were responsible for the increased macrophage EA binding and ADCC was obtained in affinity chromatography experiments in which activity could be depleted by passage over a Sepharose-Fc-coupled column and recovered in the column eluate.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1983

Latent immunoglobulin G (Gm) allotypes: occurrence in the cerebrospinal fluid in some neuropathological states.

Gm allotypes were detected and quantitated by radioimmunoassay (RIA) in paired serum and CSF samples from patients suffering from various neurological diseases. Of 115 patients with neurological disorders (65 MS and 50 others), seven subjects displayed one or two allotypes in their CSF which were absent in serum. The Gm phenotype in the patient's serum allowed us to infer the genotype without the need of familial data. A comparison of the regression curves obtained in RIA from the unexpected allotype in CSF and the counterpart in a normal serum pool argued for an identity of the Gm antigen carried by both inhibitory molecules. The unexpected allotype(s) in CSF can be considered as the product of a latent Gm gene which may be activated by either immune perturbations due to the disease per se or some particular immune regulations in the central nervous system.

Humans↗

PubMed1983

Restoration of immune responses of aging hamsters by treatment with isoprinosine.

Immune competence declines with advanced age in hamsters, as in other laboratory mammals and in humans. We found significant alterations in the functional parameters of different populations of immunocytes (natural killer cells, T cells, monocytes, and suppressor cells) in aging hamsters, beginning at approximately 14 mo of age. Natural killer cytotoxicity, phytohemagglutinin-induced lymphocyte stimulation, and monocyte chemotaxis were decreased in aging Lak:LvG(Syr) outbred hamsters. When old hamsters were given a single injection (5 mg/kg body wt) of isoprinosine, a chemical immune potentiator, these three immune parameters increased almost to the levels found in young adult hamsters but returned to pretreatment levels after 7 d. Suppressor cell activity for the lymphocyte response to phytohemagglutinin, which increased with age, was decreased after treatment. In old hamsters treated with weekly injections of isoprinosine, these four immunological parameters remained at or near the levels found in young adults.

Aging↗

PubMed1983

Association of human leukocyte antigens B7 and BW35 with sperm antibodies.

One hundred three infertile couples and 50 fertile couples were tested for the presence of sperm antibodies by passive hemagglutination and cytotoxicity assays and typed for human leukocyte antigens (HLAs) of the A and B loci. Fifty-four percent of the males and 43% of the females with sperm antibodies were found to have the HLA-B7 antigen, in contrast to 19% of a general population (P less than 0.0001). HLA-BW35 (a Workshop antigen of the B locus) was also present at a significantly increased antigenic frequency (P less than 0.00001) in those females with sperm antibodies. Of the 73 infertile couples with sperm antibodies, 79% shared the B7, B8, and/or BW35 alleles. Two of 12 infertile couples and 10 of 50 fertile couples without sperm antibodies shared these alleles. The significant association of HLA-B7 and BW35 alleles with sperm antibodies in infertile subjects suggests a selective disadvantage of these antigens in human reproduction.

Adult↗

PubMed1983

Altered heterogeneity of monocytes in acute myelomonocytic leukemia.

Human peripheral blood monocytes isolated from normal donors and patients with acute myelomonocytic leukemia (AMML) were separated on a discontinuous density gradient of bovine serum albumin (BSA) into five fractions. Cells from each fraction were assayed for cell surface markers, prostaglandin E2 (PGE2) production, ability to affect proliferation in response to antigen by autologous peripheral blood lymphocytes previously depleted of monocytes, and ability to regulate immunoglobulin (Ig) synthesis by allogeneic B-lymphocytes. Fractions 1-5 from normal donors contained 11, 10, 23, 34, and 22%, respectively, of the total number of monocytes. In contrast, in 6 patients with AMML fraction 3 was considerably larger (52%) than any other fraction, in 1 patient comprising 87% of her monocytes. Cells from each fraction differed markedly in accessory function. In general, cells from fraction 3 were poorer as helper cells than cells from other fractions. They also produced after stimulation larger amounts of PGE2 than did cells from other fractions of the gradient. These data show that PBL contain a subpopulation of monocytes, which either helps poorly or suppresses in vitro immunologic function of T-cells (proliferation) and B-cells (lg synthesis), and that this subpopulation is increased in the blood of patients with AMML.

B-Lymphocytes↗

PubMed1982

Immunoglobulin allotypes in patients with squamous cell carcinoma of the head and neck.

Gm, A2m, and Km allotypic markers were examined in 40 Caucasian patients with squamous cell carcinomas of the head and neck. Serum IgA levels, the A2m(1) allotypic marker, and antibodies against IgA1, A2m(1), and A2m(2) were measured quantitatively. The frequency of Km(1) was found to be significantly increased in patients with head and neck cancer as compared to the control population.

Adult↗