Autoimmunomodulation. Age-related opioid differences in vertebrate and invertebrate immune systems.
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Aging↗
Biomedical subjects
E M Smith
Publications and source records attributed to E M Smith.
Evidence for the conservation of an immunoreactive monokine network in invertebrates.
Mytilus edulis, a marine bivalve mollusc, contains hemocytes that share certain properties with cells of the human monocyte-macrophage lineage. Because of this and previously reported similar responses to opioids between Mytilus hemocytes and human granulocytes, we determined whether Mytilus might also possess monokines or an immune monokine-like network. We chose to study two monokines, interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF). We found that Mytilus hemocytes respond to recombinant human IL-1 and TNF in a fashion similar to human granulocytes. Furthermore, we show that as in the human system, it appears that IL-1 mediates at least part of its effects through immunoreactive (ir) TNF in Mytilus. Finally, we show that Mytilus hemolymph contains ir IL-1 and TNF. To our knowledge, this is the first demonstration of these substances in this system.
Animals↗
Immunosuppression in the definitive and intermediate hosts of the human parasite Schistosoma mansoni by release of immunoactive neuropeptides.
Evidence supporting the concept that the parasitic trematode Schistosoma mansoni may escape immune reactions from its vertebrate (man) or invertebrate (the freshwater snail Biomphalaria glabrata) hosts by using signal molecules it has in common with these hosts was obtained by the following experiments. The presence of immunoactive proopiomelanocortin (POMC)-derived peptides [corticotropin (ACTH), beta-endorphin] in, and their release from, S. mansoni was demonstrated. Coincubation of adult worms with human polymorphonuclear leukocytes or B. glabrata immunocytes led to the appearance of alpha-melanotropin (MSH) in the medium. The conclusion that this alpha-MSH resulted from conversion of the parasite ACTH by neutral endopeptidase 24.11 (NEP) present on these cells was supported by the fact that the alpha-MSH level in the medium was markedly reduced by addition of the specific NEP inhibitor phosphoramidon. This interpretation is substantiated by the fact that no conversion was observed in comparable tests with human monocytes, which exhibit no NEP activity. alpha-MSH has the capacity to inactivate formerly active immunocytes not only from the definitive host (man, hamster) but also from the intermediate host (B. glabrata), as determined by microscopic computer-assisted examination of conformational changes. POMC-derived peptides have been detected in B. glabrata hemolymph 2, 10, and 24 days after infection by S. mansoni miracidia. Immunocytes from infected snails were found to be inactivated, and this inactivation was prevented by antibodies directed against ACTH and alpha-MSH. The immunoactive beta-endorphin released from S. mansoni does not appear to be subject to enzymatic conversion. Since it is active at lower concentrations, it may be used for distant signaling.
Adrenocorticotropic Hormone↗
Immunosuppressive effects of corticotropin and melanotropin and their possible significance in human immunodeficiency virus infection.
The activation of human granulocytes and invertebrate immunocytes was found to be suppressed by corticotropin (ACTH) and melanotropin (MSH). In spontaneously active granulocytes both neuropeptides caused significant conformational changes indicative of inactivity plus a reduction in their locomotion. Significant inactivation of human granulocytes by ACTH required 2 hr, that by MSH only 20 min. The addition to the incubation medium of phosphoramidon, a specific inhibitor of neutral endopeptidase 24.11, blocked inactivation of granulocytes by ACTH. Radioimmunoassay for MSH of supernatant fluids from granulocytes incubated with ACTH demonstrated a time-dependent increase in MSH. These data strongly indicate that the effect of ACTH is largely due to its conversion to MSH by granulocyte-associated neutral endopeptidase. Parallel experiments with immunocytes from the mollusc Mytilus edulis gave similar results, indicating the universality of this phenomenon. Our finding that the human immunodeficiency virus, among several viruses, induces ACTH and MSH production in H9 T-lymphoma cells suggests an important role of these neuropeptides in the immunosuppression characteristic of such infections.
Adrenocorticotropic Hormone↗
Connective tissue activation. XXXV. Detection of connective tissue activating peptide-III isoforms in synovium from osteoarthritis and rheumatoid arthritis patients: patterns of interaction with other synovial cytokines in cell culture.
OBJECTIVE: To determine whether extracts of unincubated osteoarthritis (OA) and rheumatoid arthritis (RA) synovial tissue contain connective tissue activating peptide-III (CTAP-III) isoforms and prostaglandin E2 (PGE2), and whether such extracts have growth-promoting activity, and to determine whether binary combinations of CTAP-III with other cytokines reported to be present in synovial tissue lead to synergistic, additive, or inhibitory effects on growth. METHODS: Acid-ethanol extracts of human synovium were examined for growth-promoting activity by measuring formation of 14C-glycosaminoglycan (14C-GAG) and 3H-DNA in synovial cell cultures; PGE2 was measured by enzyme immunoassay, and CTAP-III isoforms were identified by Western blotting of extracted proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Growth-promoting activity of CTAP-III and other cytokines was tested in synovial cultures treated with the agonists singly and in binary combination, by measuring changes in synthesis of 14C-GAG and 3H-DNA. RESULTS: Platelet-derived CTAP-III and a cleavage isoform with the electrophoretic mobility of CTAP-III-des 1-15/neutrophil-activating peptide-2 (NAP-2) and PGE2 were found in biologically active extracts of synovial samples from patients with RA and OA. Five growth factors (recombinant epidermal growth factor [rEGF], recombinant interleukin-1 beta [rIL-1 beta], basic fibroblast growth factor [bFGF], PGE1, and PGE2) in binary combination with CTAP-III showed synergism in stimulating GAG synthesis; two (recombinant platelet-derived growth factor type BB [rPDGE-BB] and recombinant transforming growth factor beta [rTGF beta]) had an additive effect. In combination with CTAP-III, rEGF and rPDGF-BB had a synergistic effect in promoting DNA synthesis, rTGF beta and rbFGF had an additive effect, and rIL-1 beta, PGE1, and PGE2 were antagonistic. CONCLUSIONS: The results suggest that, in addition to endogenous factors, CTAP-III and other platelet-derived cytokines may play roles in regulating synovial cell metabolism in RA and OA, and that combinations of growth factors may be more significant than single agents in amplification or suppression of important cell functions.
Arthritis, Rheumatoid↗
Corticotropin-releasing factor-induced immunosuppression in human and invertebrate immunocytes.
1. Corticotropin-releasing factor (CRF) appears to be a potentially important signal molecule in both vertebrate and invertebrate neuroimmune and autoimmunoregulatory processes. It appears to mimic the effects of alpha-melanocyte stimulating hormone (MSH) but has a longer duration of action. 2. alpha-Helical CRF, a specific inhibitor of CRF, antagonizes CRF-induced cellular immunosuppression but is ineffective in altering MSH-induced immunosuppression. 3. Both human and Mytilus immunocytes appear to have specific CRF receptors. 4. In another experiment, both CRF and MSH antagonize tumor necrosis factor stimulation of immunocytes. Again, alpha-helical CRF antagonizes only CRF activity, further suggesting the presence of a separate CRF receptor on these cells.
Animals↗
Treatment of osseous metastases secondary to renal cell carcinoma.
Osseous metastases occur in 25 to 50% of the patients with metastatic renal cell carcinoma. We retrospectively reviewed our experience with 14 patients who underwent 20 palliative orthopedic procedures for treatment of bony metastases secondary to renal cell carcinoma. Of the patients 6 presented after nephrectomy (group 1) and 8 presented initially with osseous metastases (group 2). Only 1 of the group 2 patients underwent adjunctive nephrectomy. Overall, 5 of 14 patients (36%) presented with fracture and 9 of 14 (64%) presented with impending fracture. Five patients required multiple procedures. A total of 7 lesions had been previously treated with external radiation. Of the 20 orthopedic procedures 17 (85%) resulted in significant functional improvement and 18 (90%) resulted in significant relief of pain. There were 4 major complications in the series, including 2 culminating in amputation. Average survival after palliative orthopedic procedures was 22 months (range 7 to 64 months) with a 1-year survival rate of 58%. Orthopedic palliation of osseous metastases from renal cell carcinoma is effective, and our experience indicates that the majority of renal cancer patients with bone metastases will survive long enough to benefit from palliative orthopedic procedures.
Adult↗
Promotion of apple tree growth and fruit production by the EBW-4 strain of Bacillus subtilis in apple replant disease soil.
A field trial was conducted near Kelowna, British Columbia, to determine the effect of biological treatments alone and in combination with formalin fumigation in apple replant disease soil. The response was measured by the increase in cross-sectional trunk area, total shoot growth, and fruit yield of McIntosh apple trees on M.26 rootstock. The postplanting drench application of strain EBW-4 of Bacillus subtilis alone was consistently effective in increasing cross-sectional trunk area for 5 years, total shoot growth for 4 years, and fruit yield for 3 years. The biological agent EBW-4 of B. subtilis in combination with formalin fumigation was also effective in promoting total shoot growth and cross-sectional trunk area. The application of formalin fumigation alone was effective in increasing shoot growth for 2 years and cross-sectional trunk area for 1 year only. This treatment did not increase fruit yield for 3 years. The consistent performance of strain EBW-4 of B. subtilis during 1986-1991 indicates that this bacterium has the potential for biological control of replant disease under orchard conditions in the Okanagan Valley of British Columbia.
Bacillus subtilis↗
Hormonal activities of cytokines.
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Animals↗
Posttraumatic stress disorder among homeless men and women.
Six hundred homeless men and 300 homeless women in St. Louis were systematically interviewed using the revised Diagnostic Interview Schedule that includes a module for assessment of posttraumatic stress disorder (PTSD). Most subjects with PTSD had an additional life-time psychiatric diagnosis. No consistent pattern of association was apparent, however, between individual diagnoses and either traumatic events or PTSD. In almost three-fourths of both men and women, the onset of PTSD had preceded the onset of homelessness. Childhood histories of abuse and family fighting were predictive of both traumatic events and PTSD. The results suggest that factors leading to PTSD in the study sample began long before the onset of homelessness and may overlap with factors operative in the genesis of homelessness.
Adolescent↗
Detection of human papillomavirus infection in diseased and nondiseased sites of the respiratory tract in recurrent respiratory papillomatosis patients by DNA hybridization.
We examined 12 recurrent respiratory papillomatosis patients, who were undergoing treatment for recurrence of their disease, for the presence of human papillomavirus (HPV). Biopsies were obtained from their respiratory papillomas and nondiseased sites (NDS) of the respiratory tract: the nasopharynx, posterior tonsillar pillar, aryepiglottic fold, cervical trachea, intrathoracic trachea, and bronchi. The presence of HPV DNA was determined by using the ViraPap/ViraType DNA hybridization procedure. Two thirds of the patients were infected with HPV 6/11 in either the diseased papilloma or NDS: 50% of patients with papilloma specimens typed positive (6 of 12), and 40% of the patients typed HPV-positive in one or more biopsies from the NDS (4 of 10). No single NDS was more likely to be infected with HPV than any other. No oncogenic HPV types 16/18 or 31/33/35 were detected in the papillomas or NDS of these patients. Only patients with multiple, and not isolated, papilloma involvement were found to harbor HPV DNA in NDS; and 80% of those with infected NDS, compared to 20% of those without infected NDS, required a shorter (no more than 3 months) surgical treatment interval. Our results show that HPV infection frequently persists in adjacent, clinically normal sites, and suggest that the extent of NDS involvement may predict both the extent of disease and the likelihood of recurrence.
Adolescent↗
Immunoreactive cytokines in Mytilus edulis nervous and immune interactions.
We review evidence that an immune and nervous system linkage exists in invertebrates similar to that shown in vertebrates. Immunoreactive cytokines appear to play a role in this interaction. We have demonstrated that M. edulis, a marine bivalve mollusc, reacts to the vertebrate monokines interleukin-1, -6 and TNF. We have also demonstrated endogenous immunoreactive interleukin-1, -6 and tumour necrosis factor in M. edulis hemolymph, immunocytes and pedal ganglia. Our findings suggest an important common signalling mechanism that has been conserved over 500 million years of evolution.
Animals↗
Proopiomelanocortin-derived peptides as tools of immune evasion for the human trematode Schistosoma mansoni.
Schistosomes are digenetic trematodes which share their life cycle between a definitive (vertebrate) and an intermediate (invertebrate) host. Their survival is highly dependent on their ability to reduce significantly the efficiency of the host defences. We have previously demonstrated the presence of POMC derived peptides (ACTH, alpha-MSH, beta-endorphin) in all stages of Schistosoma mansoni life cycle. Given the immunomodulatory properties of these peptides in vertebrates and invertebrates it has been postulated that they might be implicated in parasite immune evasion. We report the release of these neuropeptides during the cycle, associated with the inhibition by these peptides of the locomotory activity of immunocytes from both hosts, the hamster Mesocricetus auratus and the freshwater snail B. glabrata. The implication of these common signals in this new strategy of parasite adaptation is discussed.
Animals↗
Resuscitation status of the elderly.
Resuscitation of patients in hospital following cardiopulmonary arrest is a standard procedure. Such intervention is not always appropriate, and this article examines some of the issues involved in making the decision not to resuscitate, with particular reference to elderly patients. The effectiveness and possible adverse effects of cardiopulmonary resuscitation (CPR) in the elderly are considered, along with ethical aspects of the problem such as how to discuss the pros and cons with the patient and relatives.
Attitude of Health Personnel↗
Lipopolysaccharide and opioids activate distinct populations of Mytilus edulis immunocytes.
Studies in Mytilus edulis have indicated that immunoregulatory activities comparable to those in vertebrates also exist in invertebrates. Mytilus immunocytes resemble cells of the vertebrate monocyte/macrophage lineage and are activated by similar substances. We searched for differential effects of opioids on these cells in comparison with those of lipopolysaccharide (LPS), in order to determine if different subpopulations of immunoactive hemocytes are involved. We showed that Mytilus immunocytes respond to LPS in a fashion similar to that in vertebrate granulocytes by flattening, and increasing in cellular perimeter and mobility, that LPS administered in vivo results in a lowering of the number of free hemocytes that can be obtained from the animal, and that distinct immunoactive cell populations seem to exist since apparently different subsets of cells react when exposed to LPS or opioids and the opioid antagonist naloxone.
Animals↗
Preparation and bioassay of connective tissue activating peptide III and its isoforms.
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Amino Acid Sequence↗
LPS stimulated invertebrate hemocytes: a role for immunoreactive TNF and IL-1.
Mytilus edulis hemocytes have similarities with vertebrate monocyte/macrophages. We have recently shown that they respond to human TNF and IL-1. We tested the possibility that Mytilus hemocytes produce similar substances in response to LPS. We show that Mytilus hemocytes respond to LPS in a fashion similar to vertebrate monocytes and macrophages and that these responses are inhibited by antibodies to TNF and/or IL-1. These findings are demonstrated both in vitro and in vivo.
Animals↗
Opioid induction of immunoreactive interleukin-1 in Mytilus edulis and human immunocytes: an interleukin-1-like substance in invertebrate neural tissue.
The synthetic analog of methionine enkephalin, [D-Ala2-Met5]-enkephalin, when administered in vitro to Mytilus edulis ganglia and hemocytes and human peripheral blood lymphocytes, induces the formation of an immunoreactive interleukin-1-like molecule. Additionally, immunoreactive interleukin-1 (IL-1) activity has been found in Mytilus nervous tissue. The stimulatory actions of the extracted immunoreactive IL-1 on Mytilus hemocytes can be antagonized by an IL-1 antibody demonstrating the specificity of the substance. The evidence suggests that the nervous system, via an opioid-IL-1 relationship, can communicate with the immune/defense system through these similar signal molecules. Furthermore, the results indicate that an interleukin-like molecule must have evolved earlier than previously thought.
Animals↗