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Biomedical subjects

W Pierpaoli

Publications and source records attributed to W Pierpaoli.

At least 55 records · Page 3Linked to original sources
PubMed1986

Role of the pineal gland in immunity. Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone.

Inhibition of synthesis of the pineal neurohormone melatonin (MEL) in mice, by administration of propranolol (PRO) in the evening, and daily injections of p-chlorophenylalanine (PCPA), resulted in a significant depression of the primary antibody response to sheep red blood cells (SRBC). Spleen cells from these mice showed a reduced reactivity against antigens in the autologous mixed lymphocyte reaction (AMLR). In contrast, alloreactivity remained normal. Reconstitution of the night-time peak of plasma MEL by evening injections to the mice completely reversed the suppression of the humoral response and the AMLR. MEL administration was able to antagonize the depression of antibody production induced by corticosterone in vivo. These results suggest that the pineal gland has important immunomodulatory functions through its cyclic, circadian release of MEL.

Animals↗
PubMed1985

Growth of transplantable melanoma and leukaemia and prevention of virus-induced leukaemia in long lived radiation chimeras constructed with unmanipulated bone marrow.

Haemopoietic radiation chimeras across the H-2 barrier (BALB/c----C57Bl/6; H-2d----H-2b chimeras and vice versa) have been studied for their capacity to suppress the growth, or to reject, transplantable B16 melanotic melanoma and radiation leukaemia virus-induced, transplantable leukaemia. Also, radiation leukaemia virus (RadLV) obtained from the thymus of leukaemic C57Bl/6 mice was injected i.p. into established chimeras (H-2d----H-2b). As expected, long lived, graft versus host disease free allogeneic chimeras constructed with intact bone marrow were unable to reject the tumours both when recipients were BALB/c----C57Bl/6 or C57Bl/6----BALB/c chimeras. However, also inoculation of a large number of immunocompetent cells from normal BALB/c mice into BALB/c----C57Bl/6 chimeras, failed to promote a rejection of the tumours. On the contrary, the same amount of syngeneic (BALB/c) immunocompetent cells prevented growth of melanoma when transferred into athymic nude BALB/c mice, while the tumour grew unimpaired in untreated athymic nude BALB/c mice. The same type of H-2d----H-2b chimeras displayed complete resistance to inculation of leukaemogenic H-2b restricted RadLV while all H-2b----H-2b, syngeneically reconstituted mice developed disseminated leukaemia. These findings demonstrate that: (a) a powerful suppressive principle operates in the chimeras which does not allow effector function and anti-tumour activity of passively transferred normal, mature T cells from resistant BALB/c mice. Thus, no H-2 restriction of donor T cells can be advocated for suppression of anti-tumour effector functions in the chimeras. (b) New donor (BALB/c, H-2d) marrow character in the H-2d----H-2b chimeras prevents expression of the H-2b restricted viral activity and leukaemogenic transformation and/or proliferation.

Animals↗
PubMed1985

Experimental manipulations and marrow-derived factors which affect the outcome of bone marrow transplantation across the H-2 barrier in lethally irradiated mice.

A system is illustrated here for transplantation of bone marrow (BMT) across the H-2 barrier in conventionally raised mice. Timing of BM inoculation after supralethal irradiation, alteration of cellular composition of BM cell inoculum, sex of donor and recipient, inoculation or removal of BM-derived supernatants, use of BM-derived factors were all variables which profoundly affected survival, hemopoietic engraftment and induction of permanent, irreversible chimerism in different strains of mice (H-2d, H-2b, H-2k) transplanted with allogeneic BM. Inoculation of BM shortly after irradiation and addition or removal of plastic-adherent cells to the BM adversely affected survival and chimerism. Also inoculation of BM in its original supernatant containing all extracellular, endogenous BM factors resulted in increased mortality. BM-derived regulating factors (MRF) exerted variable effects in different H-2 combinations. However, heat-stable components of MRF greatly affected survival and chimerism. BM-derived supernatants and MRF from rabbit or different murine H-2 types thus seem to contain powerful inhibitors and promoters of BM engraftment. Promoters stimulate allogeneic BM engraftment, are heat-resistant and non-species specific. The different character and concentration of those factors between different H-2 types is also illustrated by their in vitro effects on BM cells. These results demonstrate that different experimental manipulations and factors which do not strictly depend on genetic diversity between donor and recipient profoundly affect allogeneic BMT. Adoption of manipulations combined with use of non-T cell depleted BM and the still largely unidentified BM-derived factors result in increment of survival and lasting chimerism without any manifestation of early or late graft versus-host disease (GVHD).

Animals↗
PubMed1983

Dominance and persistence of donor marrow in long-lived allogeneic radiation chimeras obtained with unmanipulated bone marrow.

Allogeneic, H-2-incompatible irradiation chimeras (H-2d leads to H-2b) constructed with normal, unmanipulated bone marrow and with marrow-derived factors live long and do not manifest a GvH disease. Their response to primary immunization is deficient but their alloreactivity is normal. This chimeric allotolerance cannot be passively transferred from chimeric donors to normal irradiated recipients. Passive transfer of both donor- or recipient-type immunocompetent T-cells into the chimeric mice does not lead to syngeneic reconstitution, rejection of the engrafted marrow or GvH disease and the mice maintain permanently their chimerism. This new model demonstrates that chimerism is not eradicable in long-lived chimeras reconstituted with unmanipulated bone marrow, and that the bone marrow itself plays a dominant role in maintenance of chimerism.

Animals↗
PubMed1983

Allogeneic H-2d leads to H-2b irradiation bone marrow chimeras: a) failure to transfer chimerism adoptively and b) immune reactivity of immunocompetent lymphocytes adoptively transferred to chimeras.

Long-lived, GVHD-free, H-2 incompatible haemopoietic chimeras (P1 leads to P2) were constructed transfusing unmanipulated bone marrow cells together with recently identified marrow-regulating factors (MRF) in lethally irradiated recipients. The chimeric tolerance of P1 leads to P2 chimeras proved to be adoptively untransferable. Another peculiar property of established P1 leads to P2 allochimeras was their ability to "suppress" or reject passively transfused immunocompetent P1 or P2 lymphocytes. Even this "suppression" appeared to be untransferable and to operate in the chimera only in a fashion dependent upon the age of the established chimeras. This chimeric "unidentified suppressive principle" seems not to follow familiar immunologic lines. A relationship with the mechanism of chimeric tolerance is suggested.

Animals↗
PubMed1982

Host endocrine status mediates oncogenesis: leukemia virus-induced carcinomas and reticulum cell sarcomas in acyclic or normal mice.

A highly selective leukemogenic virus obtained from thymic lymphosarcomas (LS) of C57BL/6 mice was inoculated intraperitoneally into normal or gonadectomized C57BL/6 male mice and into normal or masculinized, acyclic, Charles River (CR) outbred female mice. This virus induced early onset of LS in both normal and gonadectomized C57BL/6 mice. The same virus induced a relatively late onset of many mammary adenocarcinomas in the normal CR mice and ovary adenocarcinomas and systemic neoplasms (LS and reticulum cell neoplasms) in the acyclic females. Topography, histopathology and the average latent period of the tumors were completely different between the normal and the acyclic females. This is consistent with the idea that a leukemia virus can induce tumors other than leukemia and that permanent alterations of the physiological hormonal cyclicity plays a major role in determining whether or on which target cells the ubiquitous virus will exert its carcinogenic action.

Adenocarcinoma↗
PubMed1982

Immunoreactivity of long lived H-2 incompatible irradiation chimeras (H-2d leads to H-2b).

Allogenic irradiations bone marrow chimeras made according to a new protocol with unmanipulated bone marrow are long lived, healthy and stable full chimeras (H-2d leads to H-2b). Their immunocompetence is split. Alloreactivity measured by skin graft rejection and mixed lymphocyte culture is within normal range. In contrast, major histocompatibility complex (MHC)-restricted T-cell-dependent primary responses against sheep red blood cells (SRBC) or viruses are clearly deficient. The quantitative difference in immunocompetence is at least of the order of ten-to thirty-fold. The implications of the findings for lymphohaemopoietic reconstitution of immunodeficient patients are briefly discussed.

Animals↗
PubMed1980

Why immunology?

Explore the source record for details and available documents.

Allergy and Immunology↗
PubMed1980

Factor(s) elaborated by bone marrow that promote persistent engraftment of xenogeneic and semiallogeneic marrow.

Physiological media in which bone marrow suspensions are prepared (original supernatants) contain biologically active substances which affect the engraftment of semiallogeneic or xenogeneic bone marrow in lethally irradiated recipient mice. The activity of these factors is non species-specific. When F1 hybrid mice were transplanted with parental bone marrow, a high survival rate and enduring chimerism were achieved if these marrow-derived factors were administered to the recipients. Thus, the bone marrow seems to possess an autonomous self-regulatory system represented by products of its microenvironment. Apparently, the histocompatibility barrier can be overcome when the semiallogeneic marrow is transferred to the irradiated host together with components of its own microenvironmental regulatory system.

Animals↗
PubMed1979

A new pre-irradiation conditioning regimen which protects against radiation injury and facilitates engraftment of xenogeneic bone marrow.

Administration of a large number of xenogeneic (rat) bone marrow cells before lethal, total body irradiation in mice (preconditioning regimen) results in powerful protection from radiation damage, remarkable prolongation of their survival, facilitation of marrow engraftment and induction of rat chimerism. This protective effect is not exerted by thymus or spleen cells and does not depend on specific immune mechanisms. The preconditioning regimen is more efficient when the bone marrow cells are viable and when the cells are inoculated intravenously a few hours before irradiation.

Animals↗
PubMed1978

Pharmacological control of the hormonally modulated immune response. II. Blockade of antibody production by a combination of drugs acting on neuroendocrine functions. Its prevention by gonadotropins and corticotrophin.

Injection of a combination of three drugs, 5-hydroxytryptophan, the alpha-blocker phentolamine and the neuroleptic drug haloperidol into mice before or together with sheep red blood cells (SRBC) induces a complete and long-lasting inhibition of antibody production to SRBC and leads to specific unresponsiveness. The mice unresponsive to SRBC respond normally to another antigen. Treatment with a combination of luteotropic (LH), follicle stimulating (FSH) and corticotropic hormone (ACTH) before administration of drugs and antigen prevents the immune blockade. Injection of SRBC induces an early elevation of LH in blood. This effect is prevented by previous administration of the three drugs in combination. The hormonal response to a second injection of the same antigen of mice previously made 'unresponsive' is different from that of immunized animals. The suppression of these hormonal changes which follow antigen injection by drugs acting on neuroendocrine regulation and cell membrane adrenergic receptors represents a step forward in efforts aimed at a pharmacological control of acquired immunity.

5-Hydroxytryptophan↗
PubMed1978

Pharmacologic control of the hormonally modulated immune response. III. Prolongation of allogeneic skin graft rejection and prevention of runt disease by a combination of drugs acting on neuroendocrine functions.

A recently developed pharmacologic means for suppressing acquired immunity by drugs acting on neuroendocrine regulation has been applied to transplantation immune reactions. A number of drugs have been tested singly and in combination for their capacity to suppress the immune response of mice grafted with allogeneic skin. Another model involved newborn F1 hybrid recipients inoculated with spleen cells from donors of parental strains that had been made specifically "unresponsive" by drug and alloantigen treatment. These procedures led to the identification of a combination of four drugs that induced a remarkable delay in allograft rejection and a prolonged unresponsiveness to alloantigens. This combination of drugs also abrogated the graft-vs-host-runting syndrome in newborn hybrid recipients.

Animals↗