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Biomedical subjects

D J Carr

Publications and source records attributed to D J Carr.

At least 91 records · Page 5Linked to original sources
PubMed1990

Corticotropin-releasing hormone augments natural killer cell activity through a naloxone-sensitive pathway.

Overnight treatment of murine leukocytes with corticotropin-releasing hormone (CRH) and arginine vasopressin enhances natural killer cell activity. Moreover, the opioid receptor antagonist, naloxone, as well as the delta-class opioid receptor antagonist, naltrindole, can block this effect. The responsivity of murine leukocytes to CRH is both dose- and time-dependent. The effector cells are both MAC-1 and Thy-1.2 antigen-positive. Whereas beta-endorphin is also shown to enhance natural killer cell activity in a naloxone-reversible manner, adrenocorticotropic hormone (ACTH) has a negligible effect. Macrophage depletion prior to incubation with CRH blocks the CRH-induced natural killer cell augmentation. These results suggest hypothalamic-releasing hormones such as CRH may have a biologically relevant role in the modulation of immune cells either directly or indirectly through the induction of neuropeptide hormones known to have immunomodulatory capabilities.

Animals↗
PubMed1990

Immunomodulatory characteristics of a novel antiproliferative protein, suppressin.

We investigated the immunoregulatory properties of a recently described inhibitor of lymphocyte proliferation, suppressin (SPN). It was determined that preincubation of murine leukocytes with SPN enhances natural killer cell (NK) activity. In addition, SPN potentiates interferon-gamma (IFN-gamma) augmentation of NK activity. Furthermore, preincubation of murine leukocytes with SPN induces the production of IFN-alpha/beta. The IFN-alpha/beta produced is active in NK assays as well as vesicular stomatitis virus neutralization assays. In vivo, SPN increases the time of survival of C57BL/6 mice injected with EL-4 lymphoma cells. Interestingly, SPN inhibits immunoglobulin (IgA, IgG, and IgM) production in response to the mitogen, concanavalin A in a dose-dependent manner. Collectively, the above data indicate SPN may have numerous applications in clinical science including tumor surveillance and autoimmune diseases such as arthritis.

Animals↗
PubMed1990

Bidirectional communication between the neuroendocrine and immune systems. Common hormones and hormone receptors.

The results reviewed here support a molecular basis for bidirectional communication between the immune and neuroendocrine systems. The main findings can be summarized as follows: First, cells of the immune system can synthesize biologically active neuroendocrine peptide hormones. Second immune cells also possess receptors for many of these peptides. Third, these same neuroendocrine hormones can influence immune function; and fourth, lymphokines can influence neuroendocrine tissues. The interesting conceptual advance is the idea that the immune system may serve as a sensory organ. Thus, the immune system may sense stimuli that are not recognized by the central or peripheral nervous system. These stimuli are termed noncognitive and include bacteria, viruses, tumors and antigens. The recognition of such stimuli is converted into information in the form of lymphokines, monokines, and hormones and a message received by neuroendocrine tissues. On the other hand, nervous system recognition of stimuli can also be converted into chemical signals that can be relayed to immune cells resulting in physiological changes. On this basis, we predict that the pathophysiology associated with infectious agents may be related to the types and amounts of hormones produced by the immune system.

Animals↗
PubMed1990

An antibody directed against a peptide encoded by RNA complementary to mRNA for vasopressin recognizes putative vasopressin receptors.

The purpose of this study was to generate an antibody against the binding site of the vasopressin receptor. Recently it has been demonstrated that complementary RNA sequences may encode interacting peptides. We determined whether or not an antibody directed against a peptide (PVA) specified by RNA complementary to the mRNA of rat arginine vasopressin (AVP) would recognize the AVP receptor. The antibody was purified sequentially over a protein A and then a PVA affinity column. A specific anti-PVA antibody affinity column also was made. The specific anti-PVA antibody recognized two proteins with molecular weights of 76 and 70 kD in homogenates from kidney and brain tissue containing the hypothalamus/thalamus/septum. This antibody also blocked binding of 3H-AVP to primary cultured neuronal cells, whereas the nonspecific antibody did not. Furthermore, the blocking efficiency of the antibody increased when more of the specific anti-PVA antibody was present. We also determined whether or not the antiserum contained any biological activity by observing urine volume and urine osmolality in the presence or absence of preimmune or immune serum. Only the immune serum was able to reverse the antidiuretic and urine-concentrating effects of AVP, suggesting that the antibody antagonized the effects of AVP on the kidney. Taken together with the observation that this antibody did not bind to vasopressin, these data strongly indicate that an antibody to the vasopressin receptor binding site has been made and add further support to the molecular recognition theory.

Amino Acid Sequence↗
PubMed1990

Anti-opioid receptor antibody recognition of a binding site on brain and leukocyte opioid receptors.

Opioid receptors reportedly exist on neuronal tissue of central and peripheral origin as well as on cells of the immune system. Previously, an opioid receptor has been purified from the neuroblastoma x glioma hybrid cell line, NG108-15 cells. In an effort to compare these results with opioid receptors isolated from primary neuronal tissue, we employed a methodology based on the molecular recognition theory to develop a monoclonal antibody which was used to isolate and biochemically characterize murine brain opioid receptors. We herein report the purification of an opioid receptor from mouse brain with a molecular weight of 65,000 daltons (range was 62-70 kD under reducing conditions) using a monoclonal antibody to an (the) opioid receptor. In situ labeling experiments with the delta-class selective opioid receptor affinity ligand, cis-(+)-3-methylfentanylisothiocyanate (SUPERFIT) of brain membrane confirmed these observations. Moreover, SUPERFIT, when coupled to the binding site, could block the recognition of the receptor by the monoclonal antibody. However, the selective, mu-class opioid receptor affinity reagent, 2-(p-ethoxybenzyl)-1-N,N-diethylaminoethyl-5-isothiocyanatobenz imidazole was ineffective at masking the binding site from recognition by the monoclonal antibody. Likewise, opioid-like receptors were purified from murine leukocytes which migrated at a molecular weight of 58,000 daltons under nonreducing conditions and 70,000 daltons under reducing conditions. In addition, immunoaffinity-purified receptor is shown to specifically bind the delta-class-selective opioid ligand, cis-(+)-3-methylfentanylisothiocyanate as well as the endogenous opioid peptides, beta-endorphin and [Met]-enkephalin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Monoclonal antibody against a peptide specified by [Met]-enkephalin complementary RNA recognizes the delta-class opioid receptor.

Monoclonal antibodies (MAB) were developed which recognize a peptide, His-Glu-Ala-Pro-Ile (HEAPI), encoded by the RNA complementary to the mRNA specifying [Met]-enkephalin. One such MAB (designated 6193) exhibited a high degree of reactivity to the peptide sequence. Other characteristics of 6193 MAB include: the ability to block opioid ligand binding in a radioreceptor assay; agonist activity similar to opioid peptides in suppressing cAMP production; and the recognition of a 58 kDa protein on the surface of the neuroblastoma x glioma cell line, NG108-15. These results are consistent with a reactivity of 6193 MAB with the delta-class opioid receptor.

Animals↗
PubMed1989

From the neuroendocrinology of lymphocytes toward a molecular basis of the network theory.

The cells of the immune system produce and respond to hormones that were once thought to be restricted to the neuroendocrine system. By applying a novel methodology based on the molecular recognition hypothesis, the isolation and purification of receptors shared between the immune and neuroendocrine systems was accomplished. Biochemical analysis revealed them to be virtually identical with respect to their physicochemical and functional properties. Thus, bidirectional communication between the immune and neuroendocrine systems seems to result from a common set of hormones and receptors which are shared by the two systems. Furthermore, the molecular recognition hypothesis has revealed that homologues of the binding sites of these same hormone receptor pairs may be contained within the hypervariable regions of immunoglobulins and therefore constitute part of the immunologic network.

Adrenocorticotropic Hormone↗
PubMed1989

Opioid receptors on cells of the immune system: evidence for delta- and kappa-classes.

Opioid peptides have been shown to modulate various parameters of both the humoral and cellular arms of the immune system. The modulatory capacity of the peptides can often be substantially reduced in the presence of naloxone, an opioid receptor antagonist, indicating a classical ligand-receptor interaction. In order to characterize these interactions further, we investigated the characteristics of opioid receptors on a macrophage cell line, P388d1. A delta-class opioid receptor was found with an Mr of 58,000. We also identified opioid receptors on MOLT-4 (T-cell) and IM-9 (B cell) cell lines as well as thymocytes and T cell-and B cell-enriched populations. Using the central (brain) kappa-selective agonist, U-69,593, it was also determined that P388d1 cells possess kappa-like opioid receptors. Scatchard analysis of the binding of [3H]U-69,593 revealed a single population of sites with a dissociation constant of 17 +/- 3 (S.E.M.) nmol/l and a total number of binding sites of 53.8 +/- 1.0 (S.E.M.) fmol/10(6) cells. Moreover, the racemic kappa-selective agonist U-50,488H was able to displace 50% of [3H]U-69,593 binding at 8.0 nmol/l, whereas other opioid ligands such as [Met]-enkephalinamide (delta-selective) and [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (mu-selective) were ineffective displacers of [3H]U-69,593 except at high concentrations.

Animals↗
PubMed1989

Hormones common to the neuroendocrine and immune systems.

Considerable progress is now being made in studies of the interactions between the immune and neuroendocrine systems, and the relevance of the results to many disease processes is increasingly recognised. Recent published, and hitherto unpublished, work on one aspect of this topic--the production and function of neuroendocrine hormone by cells of the immune system--is herein summarised by a foremost investigator and his colleagues. Evidence is presented that several peptide hormones (ACTH, endorphins, thyrotropin, chorionic gonadotropin, growth hormone) are produced constitutionally, or in response to stimulation, by cells of the immune system, and there is speculation as to their roles in local immune response, endotoxic shock, antibody production, pregnancy, and in the diagnosis of specific psychiatric and neuroendocrine disorders. The review and commentary contribute to fuller understanding of the underlying molecular biology, from which new opportunities in rational drug design will undoubtedly emerge.

Animals↗
PubMed1988

Evidence for a delta-class opioid receptor on cells of the immune system.

Opioid receptors have been reported to be present on cells of the immune system. Both opioid receptor-ligand interactions which are reversible by naloxone (classical) and those interactions which are irreversible by naloxone (nonclassical) appear to alter various immunologic parameters through the ligand-receptor interactions. In an effort to characterize opioid receptors (which operate with classical interactions) on cells of the immune system, we employed the delta-class opioid receptor-specific ligand, cis-(+)-3-methylfentanylisothiocyanate (SUPERFIT). We herein report the specific labeling of a protein with a molecular weight of 70,000 Da under reducing conditions (58,000 Da under nonreducing conditions) from both B and T cell-enriched murine splenocytes and peripheral blood lymphocytes. Similar results are demonstrated by human peripheral blood lymphocytes and plastic-adherent (monocyte-enriched) leukocytes.

Animals↗
PubMed1988

The production of antibodies which recognize opiate receptors on murine leukocytes.

An antibody has been developed which recognizes opiate receptors on cells of the immune system. This antibody blocks specific binding of the radiolabeled opiate receptor ligand, 3H-dihydromorphine, to receptors on murine splenocytes. Additionally, the anti-receptor antibody competes with beta-endorphin, met-enkephalin, and naloxone for the same binding site on the leukocytes. Moreover, the anti-receptor antibody possesses agonist activity similar to beta-endorphin in suppressing cAMP production by lymphocytes. These results suggest the development of an antibody which recognizes classical opiate receptors on cells of the immune system.

Animals↗
PubMed1988

"Classical" neuroendocrine peptide hormones produced by cells of the immune system.

Cells of the immune system are shown to produce peptide hormones whose production was once thought to be restricted to neuroendocrine tissue. Interestingly, in some cases, very specific stimuli elicit the production of one species of neuropeptide hormone. In other instances, it appears that some peptide hormones are constitutively produced. In either situation, the various immunocyte-derived hormones have biological activity in endocrinological assays. In the present report, a review of the various neuroendocrine hormones produced by cells of the immune system is discussed.

Animals↗
PubMed1987

Immunoaffinity-purified opiate receptor specifically binds the delta-class opiate receptor ligand, cis-(+)-3-methylfentanylisothiocyanate, SUPERFIT.

Using an antibody generated against the opiate receptor on NG108-15 cells, we recently purified the putative receptor from this hybrid cell line. We herein report that the purified receptor complex specifically binds tritiated cis-(+)-3-methylfentanylisothiocyanate (SUPERFIT), with the predominant binding associated with a 58 kDa polypeptide chain. Consistent with these findings is the in situ labeling of a 58 kDa protein with [3H]SUPERFIT on NG108-15 cells.

Animals↗
PubMed1986

An antibody to a peptide specified by an RNA that is complementary to gamma-endorphin mRNA recognizes an opiate receptor.

The putative delta-opiate receptor complex has been identified by a new approach which employed an antibody that is directed against a peptide which binds gamma-endorphin and is specified by RNA that is complementary to that of gamma-endorphin mRNA. This antibody competes with beta-endorphin and naloxone for binding sites on the surface of neuroblastoma X glioma NG108-15 hybrid cells. The opiate receptor complex has an apparent molecular weight of 210,000 and is composed of four noncovalently associated subunits with apparent molecular weights of 68,000, 58,000, 45,000 and 30,000.

Antibodies↗
PubMed1986

Enhancement of the generation of cytotoxic T cells by endogenous opiates.

Previous reports have shown that endogenous opiates (beta-endorphin and met-enkephalin) have effects on cells of the immune system at physiologic concentrations. Using murine spleen cells, we herein report that beta-endorphin and met-enkephalin can enhance the generation of cytotoxic T lymphocytes (CTLs) at suboptimal concentrations of alloantigen in a one-way mixed lymphocyte culture (MLC). This enhancement is seen at levels ranging from 2.9 X 10(-8) M to 2.9 X 10(-14) M and 1.45 X 10(-6) M to 1.45 X 10(-12) M for beta-endorphin and met-enkephalin, respectively. This enhancement can be partially blocked by naloxone at 10(-7) M. Furthermore, the simultaneous addition of met-enkephalin and beta-endorphin does not increase the enhancement of CTL generation by either opiate peptide alone suggesting that they are acting through the same receptor. This report gives added proof for the regulatory-loop theory between the neuroendocrine and immune systems.

Animals↗