Endorcine cells producing regulatory peptides

Summary Recent data on the immunologication of regulatory peptides and related propeptide sequences in endocrine cells and tumours of the gastrointestinal tract pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory beenrevised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptidesare the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, -MSH and CLIP (corticotropoin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenalin-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.     

Preliminary observations on the co-existence of regulatory peptides in cells of the baboon endocrine pancreas

Summary Immunocytochemical procedures at ultrastructural and light microscopy level revealed, in the Chacma baboon endocrine pancreas, cells which were immunoreactive for glucagon and pancreatic polypeptide (PP). Some D cells were observed to contain secretory granules with both the appearance and immunoreactivity of A cell secretory granules.     

Preliminary observations on the co-existence of regulatory peptides in cells of the baboon endocrine pancreas

Immunocytochemical procedures at ultrastructural and light microscopy level revealed, in the Chacma baboon endocrine pancreas, cells which were immunoreactive for glucagon and pancreatic polypeptide (PP). Some D cells were observed to contain secretory granules with both the appearance and immunoreactivity of A cell secretory granules.     

Precursors to regulatory peptides: their proteolytic processing

Summary Precursors to regulatory peptides undergo maturation processes which include protelytic processing. The enzymes involved in this process remove the hydrophobic peptide located at the amino-terminus of the precursor. Endoprotease cleavage also occurs at single and two adjacent basic residues, this is followed by a removal of basic residues located at the C-terminus of the peptides by a carboxypeptidase-like enzyme.     

Aspects of measurement and analysis of regulatory peptides

Summary Although almost all methods of mass measurement of regulatory peptides still depend on the high affinity antibody, the traditional Yalow and Berson radioimmunoassay technique is becoming outdated. Pure monoclonal antibodies allow excess antibody two site assay techniques with a variety of different labels (preferentially non-radioactive) of great sensitivity and speed. The large amounts of particular monoclonal antibodies available allow several different laboratories to use the same reagents and have increased comparability. Unfortunately many regulatory peptides exist in multiple molecular forms and attention must be paid to antibody region specificity. Improved methods of extraction of regulatory peptides from plasma tissue allow more accurate quantitation. New techniques for rapid high resolution chromatography make distinction of different molecular forms much easier than hitherto. Better education in techniques and/or attention to inter-assay standards are necessary to improve the comparability of regulatory peptide measurement in the future.     

Precursors to regulatory peptides: their proteolytic processing

Precursors to regulatory peptides undergo maturation processes which include proteolytic processing. The enzymes involved in this process remove the hydrophobic peptide located at the amino-terminus of the precursor. Endoprotease cleavage also occurs at single and two adjacent basic residues, this is followed by a removal of basic residues located at the C-terminus of the peptides by a carboxypeptidase-like enzyme.     

Cationic host defence peptides: Innate immune regulatory peptides as a novel approach for treating infections

An increase in antibiotic resistance and the emergence of new pathogens has led to an urgent need for alternative approaches to infection management. Immunomodulatory molecules that do not target the pathogen directly, but rather selectively enhance and/or alter host defence mechanisms, are attractive candidates for therapeutic development. Natural cationic host defence peptides represent lead molecules that boost innate immune responses and selectively modulate pathogen-induced inflammatory responses. This review discusses recent evidence exploring the mechanisms of cationic host defence peptides as innate immune regulators, their role in the interface of innate and adaptive immunity, and their potential application as beneficial therapeutics in overcoming infectious diseases. Received 3 November 2006; received after revision 14 December 2006; accepted 22 January 2007     

The endocrine role for chromogranin A: A prohormone for peptides with regulatory properties

Chromogranin A (CgA) belongs to the granin family of uniquely acidic secretory proteins co-stored and co-secreted with other hormones and peptides in elements of the diffuse neuroendocrine system. The granins arise from different genes and are characterized by numerous sites for post-translational cleavage into shorter peptides with postulated regulatory properties. This review is directed towards endocrine aspects of CgA and its biologically active peptides. There is ample evidence from in vitro studies of distinct effects and targets for three CgA-derived peptides, vasostatin-I, pancreastatin and catestatin. Endocrine regulations are indicated from in vivo studies, consistent with the postulated prohormone function of CgA for peptides with regulatory properties. Most of the effects fit into patterns of direct or indirect, inhibitory modulations of major functions, implicating CgA peptides in regulation of calcium and glucose metabolism, cardiovascular functions, gastrointestinal motility and nociception, tissue repair, inflammatory responses and as host defense peptides in the first phase of microbial invasions. Received 1 June 2007; received after revision 11 July 2007; accepted 12 July 2007     

The development and function of regulatory T cells

Regulatory T cells (Tregs) are a critical subset of T cells that mediate peripheral tolerance. There are two types of Tregs: natural Tregs, which develop in the thymus, and induced Tregs, which are derived from naive CD4⁺ T cells in the periphery. Tregs utilize a variety of mechanisms to suppress the immune response. While Tregs are critical for the peripheral maintenance of potential autoreactive T cells, they can also be detrimental by preventing effective anti-tumor responses and sterilizing immunity against pathogens. In this review, we will discuss the development of natural and induced Tregs as well as the role of Tregs in a variety of disease settings and the mechanisms they utilize for suppression. C. J. Workman, A. L. Szymczak-Workman, L. W. Collison, and M. R. Pillai contributed equally.     

Epidermal growth factor stimulates proliferation of rat hepatoma cells producing alpha-fetoprotein.

Epidermal growth factor stimulated both [3H]thymidine uptake and proliferation of rat AH66 hepatoma cells. However, the increase in cell number was not accompanied by a proportional increase in the levels of alpha-fetoprotein of the culture media. The effects of EGF on the cell proliferation were antagonized by N6,O2'-dibutyryl cAMP.     

Heat shock protein 60: regulatory role on innate immune cells

Human heat shock protein 60 (Hsp60) exhibits immunoregulatory properties, primarily by inducing pro-inflammatory responses in innate immune cells. Extensive analyses identified specific receptor structures for the interaction of Hsp60 with these cells. The existence of distinct receptor structures responsible for Hsp60 binding and for Hsp60-induced release of pro-inflammatory mediators has been demonstrated, implying that the interaction of Hsp60 with innate immune cells is a multifaceted process. Distinct Hsp60 epitopes responsible for binding to innate immune cells and for the activation of these cells have been identified. Depending on the cell-type, the amino acid (aa) region 481–500 or the regions aa241–260, aa391–410 and aa461–480 are involved in Hsp60-binding to innate immune cells. An entirely different Hsp60-region, aa354–365 was found to bind lipopolysaccharide, thereby mediating the pro-inflammatory effects of Hsp60. Because of its immunoregulatory properties, Hsp60 has been proposed to act as intercellular danger signal, controlling innate and adaptive immune reactions. Received 19 September 2006; received after revision 13 October 2006; accepted 13 December 2006     

Endocrine cells in mammalian gastric mucosa: Possible storage sites for vitamin B12-binding proteins

Zusammenfassung Es wird angenommen, dass in Maus, Ratte, Hamster und Meerschweinchen Vitamin B₁₂-bindende Proteine sich mit enterochromaffinähnlichen (argyrophilen, nichtargentaffinen) Zellen und im Kaninchen mit einer bestimmten Art enterochromaffiner (argentaffiner) Zellen verbinden.     

The battle against immunopathology: infectious tolerance mediated by regulatory T cells

Infectious tolerance is a process whereby one regulatory lymphoid population confers suppressive capacity on another. Diverse immune responses are induced following infection or inflammatory insult that can protect the host, or potentially cause damage if not properly controlled. Thus, the process of infectious tolerance may be critical in vivo for exerting effective immune control and maintaining immune homeostasis by generating specialized regulatory sub-populations with distinct mechanistic capabilities. Foxp3(+) regulatory T cells (T(regs)) are a central mediator of infectious tolerance through their ability to convert conventional T cells into induced regulatory T cells (iT(regs)) directly by secretion of the suppressive cytokines TGF-β, IL-10, or IL-35, or indirectly via dendritic cells. In this review, we will discuss the mechanisms and cell populations that mediate and contribute to infectious tolerance, with a focus on the intestinal environment, where tolerance induction to foreign material is critical.     

The prolactin releasing peptides: RF-amide peptides

Although dopamine is considered the major hypothalamic controller of prolactin release from the anterior pituitary gland, there is evidence that a yet to be discovered prolactin releasing factor (PRF) also exists in brain. Recently, two peptides were isolated, products of the same prohormone, that were reported to have significant prolactin-releasing activity. These peptides, called prolactin releasing peptides, are not accepted by all investigators to be in fact PRFs. Instead, it appears that their widespread distribution in brain and the presence of receptors for the peptides in sites unrelated to neuroendocrine function are the basis for a variety of central nervous system action including activation of the autonomic nervous system. Thus, these peptides may not be PRFs, but instead neuroactive agents that are involved in many brain circuits with divergent functions.     

Synthetic peptides related to eledoisin. Physalaemin-like peptides

Riassunto Vengono riportate le proprietà di una serie di peptidi sintetici affini per struttura alla fisalemina.