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D M Murasko

Publications and source records attributed to D M Murasko.

At least 73 records · Page 4Linked to original sources
PubMed1985

Poly I:C or IFN-alpha/beta treatment inhibits macrophage induced T cell proliferation.

IFN-alpha/beta has been previously shown to cause the suppression of various immune responses. The reason for this immunosuppression, however, remains unknown. The studies described in this report demonstrate that treatment of mice with poly I:C or partially purified IFN alpha/beta inhibited the ability of KLH pulsed macrophages to induce proliferation of KLH immune T cells. This failure to generate antigen induced proliferation was not caused by the production of prostaglandins or other suppressive molecules by IFN treated macrophages, nor did this treatment induce suppressor macrophages.

Animals↗
PubMed1985

Biological similarities of rat fibroblast interferon to human and mouse alpha interferons.

High titres of rat interferon (IFN) can be produced by rat embryo fibroblast (CD) cells after treatment with Newcastle disease virus. This CD IFN was characterized by SDS-PAGE, and was found to contain three species at 30K to 33K, 25K to 27K and 17K to 22K mol. wt. Antibody affinity chromatography revealed that 95% of the CD IFN bound to an anti-human leukocyte IFN antibody column, 34% to an anti-mouse L cell IFN antibody column and none to an anti-human fibroblast IFN antibody column. The IFN that bound to the anti-human leukocyte IFN antibody column contained all three molecular weight species of IFN. However, the material bound to the anti-mouse L cell IFN antibody column only showed IFN activity of the 30K and 20K species. Examination of the heterologous antiviral activity of the unseparated CD IFN and of the IFN separated by antibody affinity chromatography revealed the same patterns of activity: 35 to 50% of homologous activity on guinea-pig cells, 10 to 20% on mouse cells, 2 to 4% on human cells and none on bovine cells. The data suggest that a major portion of this rat fibroblast IFN is related to alpha IFNs produced by other species.

Animals↗
PubMed1985

Comparative effects of various classes of mouse interferons on macrophage activation for tumor cell killing.

The effects of mouse interferon-alpha (MuIFN-alpha), -beta (MuIFN-beta), and -gamma (MuIFN-gamma) on macrophage activation for tumor cell killing were determined by using proteose peptone-elicited peritoneal macrophages from C3H/HeN and C3H/HeJ mice under conditions that either included or were free of detectable endotoxin. Alone, under the conditions used, none of the interferons was able to activate macrophages directly for tumor cell killing. However, with a second signal provided to responsive macrophages by contaminating endotoxin, added bacterial lipopolysaccharide (LPS), or heat-killed Listeria monocytogenes (HKLM), all three types of interferon induced cytolytic activity, with MuIFN-gamma approximately 500 to 1000-fold more active than either MuIFN-alpha or -beta. Thus, all three interferons were able to prime macrophages for killing but required a second signal before cytolytic activity could be expressed. When MuIFN-gamma was mixed with either MuIFN-alpha or -beta and placed on macrophages, little or no killing developed. Mixtures of MuIFN-gamma with either MuIFN-alpha or -beta did increase the sensitivity of macrophages to triggering by LPS, however, compared with macrophages treated with MuIFN-gamma alone. The results are collectively important because they i) confirm that significant quantitative differences exist between the various interferons with regard to their capacity to prime macrophages for tumor cell killing; ii) indicate that to be an efficient activator each type of interferon must be combined with a second stimulus, such as LPS or HKLM; iii) show that neither MuIFN-alpha nor -beta can provide an efficient second triggering signal for macrophages that are primed by MuIFN-gamma; and iv) document that mixtures of MuIFN-gamma with either MuIFN-alpha or -beta are most efficient at inducing priming, compared with any one of the interferons used alone.

Animals↗
PubMed1984

Production and partial purification of rat fibroblast-derived interferon induced in a newly established cell line.

Interferon (IFN) production induced by either Newcastle disease virus (NDV) or Sendai virus was compared in 10 different rat cell lines. Although there was variation in the IFN titers produced, NDV proved to be the best inducer in each cell line with optimum IFN yields occurring with a multiplicity of infection (MOI) of 1.0. A new continuous rat fibroblast cell line (CD) produced high titers of IFN similar to those reported for other high producers; while Ratec cells were shown to be the most sensitive to the antiviral activity of rat IFN. Partial purification and characterization of IFN produced in CD cells was accomplished by column chromatography. Four sorbents with varying modes of action for binding the IFN (Affi-Gel 202, Poly(U)-Sepharose 4B, CM-Sepharose CL-6B, and Phenyl-Sepharose CL-4B) were compared. The Phenyl-Sepharose CL-4B matrix proved to be the most successful for purification of rat IFN; one passage through this column, increased the specific activity more than 100-fold, with a concomitant recovery of 90%-95% biologic activity. The binding characteristics of rat IFN on each of the column matrices, however, demonstrated differences between the physicochemical nature of CD rat IFN and murine and hamster IFNs.

Animals↗
PubMed1984

Genetic control of neutralizing antibody response to mouse interferon in rats.

Various strains of rats were immunized weekly with mouse interferon (IFN containing both IFN-alpha and IFN-beta). Their sera were examined for the ability to neutralize the antiviral activity of IFN in a microtiter assay. DA and ACI (RT-1a), BN (RT-1n), and WF (RT-1w) strains of rats produced anti-IFN antibodies after a minimum of four inoculations. In contrast, neither Lewis (RT-1l) nor Buffalo (RT-1b) strains of rats produced any detectable anti-IFN antibodies even after 12 weekly inoculations of IFN. This lack of responsiveness could not be overcome by immunization in the presence of Freund's complete adjuvant. The genetic basis of this difference in antibody response was examined using F1 and back-cross generations of rats. Both (ACI X LEW) F1 and (LEW X ACI) F1 rats produced titers of anti-IFN antibody intermediate to the parental strains. No maternal or paternal effects were observed. Results from the back-cross generation of F1 rats to the parental strains suggested that although the major histocompatibility complex may be a factor in control of this response, other genes are also involved.

Animals↗
PubMed1984

Genetic variation in the ability of several strains of rats to produce interferon in response to polyriboinosinic-polyribocytodilic acid.

The ability of various strains of rats to produce interferon in response to polyriboinosinic-polyribocytodilic acid was investigated. ACI and DA (RT-1a), BN (RT-1n), Buffalo (RT-1b), August (RT-1c), and GH (RT-1l) strains produced low levels of interferon in response to intraperitoneal administration of polyriboinosinic-polyribocytodilic acid. However, Lewis (RT-1l) rats demonstrated a 20- to 40-fold higher response. The genetic basis of this difference in production was examined through use of F1 and backcross generations of rats. Both (ACI X Lewis) and (Lewis X ACI) F1 rats exhibited levels of interferon production intermediate to those of the parental strains. No maternal or paternal effects were observed. Results with the F1 rats and the wide variation of response also observed in the backcross generations of F1 rats to either low (ACI) or high (Lewis) responders suggested that several loci control the ability of these rats to produce interferon. Compatibility at the RT-1 locus in both low and high responders negates any significant involvement of the major histocompatibility complex in this control.

Animals↗
PubMed1983

Enhancement or inhibition of tumor growth by interferon: dependence on treatment protocol.

MSC cells are tumor cells originally induced in BALB/c mice by Moloney sarcoma virus. In these studies we demonstrated that, although these tumor cells are sensitive in vitro both to lysis by NK or NK-like cells and to the growth-inhibitory effect of murine L-cell interferon (IFN), the growth of the tumor in vivo could be either inhibited or enhanced by IFN. The outcome of in vivo IFN treatment was dependent on the timing and route of IFN administration relative to tumor challenge. IFN given systematically at the same time as tumor challenge resulted in enhancement of primary tumor formation, rate of tumor growth and subsequent progressive tumor growth. In contrast, IFN administered at the site of tumor inoculation on days 1-3 after tumor challenge inhibited tumor formation and growth. Histopathology of tissue sections obtained from the site of tumor challenge confirmed these results. Similar studies performed in mice given 450 rads of X-irradiation showed that IFN could still inhibit tumor growth when administered at the site of tumor inoculation on days 1-3 after tumor challenge. IFN administered simultaneously with tumor challenge, however, did not enhance tumor growth in irradiated mice. These results are consistent with the interpretation that 1) inhibition of MSC-induced tumor growth by IFN has a radioresistant component and 2) the enhancement of MSC-induced tumor formation by IFN is dependent on interaction with a radiosensitive population of cells, possibly lymphoid cells.

Animals↗
PubMed1983

Production, screening and characterization of a monoclonal antibody to murine interferon-beta.

A hybrid murine myeloma (2-13F5) secreting a monoclonal antibody that specifically bound and neutralized murine interferon beta has been isolated. Affinity chromatography with immobilized 2-13F5 monoclonal antibody of murine IFN (containing both IFN-alpha and IFN-beta) separated an IFN-beta preparation that demonstrated one band with Coomassie Brilliant Blue staining of SDS-PAGE at a molecular weight of 35000 and a specific activity of 4.3 x 10(8) units/mg of protein. This monoclonal antibody neither bound nor neutralized murine IFN-alpha. In addition, it bound only 87% of the interferon demonstrating a molecular weight of 35K. Possible explanations of this partial binding are discussed.

Animals↗
PubMed1983

Effect of interferon on thoracic duct lymphocyte output: induction with either poly I:poly C or vaccinia virus.

Systemic inoculation of the interferon (IFN) inducer polyinosinic-polycytidylic polyribonucleotide (poly I:poly C) into CBA/J mice produces a significant decrease in the number of thoracic duct lymphocytes (TDL) collected 6 to 22 hr after injection. The number of TDL is restored to normal levels by 48 to 64 hr. Residual TDL collected during the inhibition period of poly I:poly C treatment showed a phenotypic profile similar to phosphate-buffered saline- (PBS) treated control groups when examined for Lyt-1.1, Lyt-2, Thy-1.2 and Iak surface markers. Interferon is implicated as the mediator of this phenomenon since: 1) Inoculation of exogenous IFN can induce a similar suppression in the number of recoverable TDL. 2) Pretreatment of mice with sheep anti-murine IFN serum can block this effect of poly I:poly C. Similar experiments with vaccinia virus demonstrate that although live virus can partially suppress the TDL output, almost complete suppression is achieved with ultraviolet (UV)-inactivated virus. Vaccinia virus-induced suppression of the number of TDL also appears to be caused by IFN since: 1) UV-inactivated virus induces significantly higher serum levels of IFN in comparison to live virus. 2) The suppression of TDL output by either live or UV-inactivated vaccinia virus can be blocked by pretreatment with anti-murine IFN. These findings suggest that the immunosuppression often associated with viral infections may be at least partially due to a decrease in lymphocyte recirculation mediated by the IFN initially released in response to the virus.

Animals↗
PubMed1981

Effect of anti-interferon serum on Friend virus infection and Fv-1-mediated resistance.

The purpose of these studies was (1) the quantitation of the protective effect of endogenous interferon (IFN) in the Friend virus (FV) system, and (2) the determination of the role of IFN in the relative resistance to FV mediated by the Fv-1-gene. In these studies, mice from two strains differing with respect to their Fv-1 alleles were treated with sheep anti-mouse IFN serum immediately prior to infection with N-tropic FV. The effect of this pretreatment showed that the neutralization of FV-induced IFN by anti-IFN resulted in a two to tenfold increase in susceptibility to FV infection as measured by the appearance of macroscopic foci of erythroleukemic cells on the splenic surface as compared to control mice which received normal sheep serum. At higher virus doses, an increase in spleen weight in anti-IFN-treated mice was also observed. Mice resistant to FV by virtue of their Fv-1 allele were affected by anti-IFN pretreatment only as much as mice from the susceptible strain. Therefore, IFN appeared to play no role in Fv-1-mediated resistance.

Animals↗
PubMed1980

Induction of interferon in AKR mice by murine leukaemia viruses.

A high percentage of AKR mice develop spontaneous leukaemia which has shown to be associated with the early expression of ecotropic murine leukaemia virus (MuLV) and the subsequent expression of xenotropic as well as polytropic MuLVs. Generally, mice infected with any one of several groups of viruses, including MuLVs, have been shown to produce interferon (IF). However, we report here that AKR mice produce no IF, despite that fact that infectious, endogenous MuLV is expressed in these mice from birth.

AKR murine leukemia virus↗
PubMed1978

Stimulatory effect of immunization on tumor induction by Moloney murine sarcoma virus.

Adult mice were immunized with varying doses of inactivated Moloney murine leukemia virus (M-MuLV). Eight weeks after immunization, mice were challenged with a dose of Moloney murine sarcoma virus (M-MuSV) that could induce tumors in approximately 50% of normal animals. Mice immunized with high doses of M-MuLV (10(10) particles) had significantly decreased tumor incidences, whereas mice immunized with low doses of M-MuLV (10(2) particles) had significnatly increased tumor incidences compared to those in nonimmunized controls. The stimulatory effect could be abrogated by the irradiation of mice with 450 rads 24 hours prior to M-MuSV challenge, whereas the inhibitory effect was resistant to this irradiation procedure. The results suggested that immunization with virus can either stimulate or inhibit virus-induced tumorigenesis, depending on the dose of virus used for immunization.

Animals↗
PubMed1978

Apparent lack of H-2 restriction of allograft rejection.

BALB/c ByJ (H-2d) mice immunized with tail skin grafts of either B10.D2 (H-2d) or B10 (H-2b) demonstrated similar second set rejection of B10.D2 tail skin. This apparent lack of H-2 restriction was not due to the induction of a new population of cytotoxic T lymphocytes (Tc) since 450R given 24 hr before the challenge graft did not abrogate the second set reactivity. Host macrophage processing or anti-Qa-2 reactivity was also not the explanation for the lack of H-2 restriction since immunization of BALB/c Li mice with either B10.D2 or B10 tail skin grafts resulted in second set rejection of B10 tail skin. Shared public H-2 specificities of H-2d and H-2b may result in cross-reactive Tc, thus causing the apparent lack of H-2 restriction. However, no H-2 restriction of allograft rejection is observed when only one public H-2 specificity is shared between the recipient and the allogeneic challenge graft (H-2f and H-2k combination). These results suggest that H-2 restriction of T cell cytotoxicity has little relevance in allograft rejection because 1) one public H-2 specificity is sufficient to cause cross-reactivity or 2) Tc are not the major effectors of allograft rejection.

Animals↗
PubMed1975

Spleen-cell cytotoxicity for cytomegalovirus-transformed cells. II. Inhibition by cytomegalovirus antiserum.

Serum from hamsters immunized repeatedly with cytomegalovirus (CMV) was able to block spleen-cell cytotoxicity for CMV-infected and CMV-transformed cells. Inhibition was observed regardless of whether spleen cells were obtained from hamsters sensitized to the virus or to isografts of the transformed cells (designated Cx-90-3B, T-2). Such serum did not significantly block effector cell response against transformed cells expressing herpes simplex virus or SV40-associated membrane antigens. The mechanism of blocking was investigated. It was found that the blocking activity could be adsorbed out with Cx-90-3B, T-2 cells but not by untransformed hamster embryo fibroblasts. Cx-90-3B, T-2 target cells treated with serum, and then washed, remained resistant to effector cell attack. On the other hand, if serum-treated attacker cells were washed their cytotoxic activity was not significantly impaired. These results suggest that the blocking factor in the serum is antibody-directed against cytomegalovirus-related membrane antigen. This conclusion is supported by the finding that the serum contained antibody specifically reactive with the transformed cell surface in isotopic antiglobulin tests.

Animals↗