Mitogenic activation of the human lymphocytes induce the release of proenkephalin derived peptides

Padros, Maria Rosa; Vindrola, Osvaldo; Zunszain, Patricia A.; Fainboin, Leonardo; Finkielman, Samuel; Nahmod, Víctor E.

doi:10.1016/0024-3205(89)90521-3

Cited by 24 publications

(12 citation statements)

References 21 publications

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“…Another line of research revealed that lymphoid cells express opioid-encoding genes and release products which have previously been considered to be exclusively of neuroendocrine origin. PENK mRNA and PENK-derived peptides in the immune system were demonstrated in murine T helper cell lines, in leukocytes of leukemia patients, in normal rat lymphocytes, and in rodent and human mononuclear phagocytes [Zurawski et al, 1986;Monstein et al, 1986;Padros et al, 1989;Rosen et al, 1989;Linner et al, 1991;Kuis et al, 19911. A recent report demonstrated that PENK expression by monocytes is induced by endotoxin [Behar et al, in press], and that the monocyte-derived enkephalins interact with receptors on sensory nerves to inhibit nociception of inflamed tissues [Stein et al, 1990;Przewlocki et al, 19921.…”

Section: O P L O L D System In the Periphery A N D The Control Of Painmentioning

confidence: 99%

Dual role of osteoblastic proenkephalin derived peptides in skeletal tissues

Rosen

Bar‐Shavit²

1994

J of Cellular Biochemistry

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Proenkephalin encode a group of small peptides with opiate-like activity, the endogenous opioids, known to function as neurohormones, neuromodulators, and neurotransmitters. Recently, we have demonstrated that in addition to its abundance in fetal brain tissue, proenkephalin is highly expressed in nondifferentiated mesodermal cells of developing fetuses. We identified the skeletal tissues, bone, and cartilage as major sites of proenkephalin expression. To examine the possibility that proenkephalin is involved in bone development we have studied the expression of this gene in bone-derived cells, its modulation by bone active hormones, and the effects of enkephalin-derived peptides on osteoblastic phenotype. Our studies revealed that osteoblastic cells synthesize high levels of proenkephalin mRNA which are translated, and the derived peptides are secreted. Reciprocal interrelationships between osteoblast maturation and proenkephalin expression were established. These results together with our observations demonstrating inhibitory effects of proenkephalin-derived peptides on osteoblastic alkaline phosphatase activity, strongly support the notion that proenkephalin is involved in bone development. A different direction of research by other investigators has established the capability of the opioid system in the periphery to participate in the control of pain. On the basis of these two lines of observation, we would like to present the following hypothesis: The potential of embryonic skeletal tissue to synthesize proenkephalin-derived peptides is retained in the adult in small defined undifferentiated cell populations. This potential is realized in certain situations requiring rapid growth, such as remodeling or fracture repair. We suggest that in these processes, similarly to the situation in the embryo, the undifferentiated dividing cells produce the endogenous opioids. In the adult these peptides may have a dual function, namely participating in the control of tissue regeneration and in the control of pain.

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Section: O P L O L D System In the Periphery A N D The Control Of Painmentioning

confidence: 99%

Dual role of osteoblastic proenkephalin derived peptides in skeletal tissues

Rosen

Bar‐Shavit²

1994

J of Cellular Biochemistry

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“…Moreover, locally synthesized enkephalins in inflamed tissues could produce interstitial enkephalin concentrations much higher than those observed in plasma. The concept of local enkephalin is supported by the finding that inflammatory cells contain enkephalins and the mRNA for their precursor, proenkephalin (Padrós et al 1989;Przewlocki et al 1992;Rittner et al 2001). Furthermore, enkephalins undergo rapidly hydrolysis, underestimating the actual concentration.…”

Section: Discussionmentioning

confidence: 91%

“…Opioid peptides, including enkephalins, are present at inflammation sites (Padrós et al 1989;Sibinga and Goldstein 1988;Vindrola et al 1990). During inflammatory process, the migration of opioid-containing leukocytes to inflamed tissues is induced.…”

Section: Introductionmentioning

confidence: 98%

Oxidative and nitrative modifications of enkephalins by human neutrophils: effect of nitroenkephalin on leukocyte functional responses

et al. 2011

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Neutrophils play a major role in acute inflammation by generating reactive oxygen/nitrogen species. Opioid peptides, including enkephalins, are present at inflammation sites. Neutrophils contribute to protect against inflammatory pain by releasing opioid peptides. In this investigation, the ability of human polymorphonuclear cells to induce oxidative and nitrative modifications of Leu-enkephalin has been investigated in vitro. Activated human neutrophils mediate the oxidation of Leu-enkephalin resulting in the production of dienkephalin. In the presence of nitrite at concentrations observed during inflammatory and infectious process (10-50 μM), nitroenkephalin, a nitrated derivative of Leu-enkephalin, is additionally formed. The yield of nitroenkephalin increases with nitrite concentration and is significantly inhibited by the addition of catalase or 4-aminobenzoic acid hydrazide (ABAH), a specific inhibitor of peroxidases. These results suggest that neutrophils induce nitration of Leu-enkephalin by a mechanism that is dependent on myeloperoxidase activity and hydrogen peroxide. Oxidative/nitrative modifications of Leu-enkephalin have been also evidenced when cells were treated with the NO-donor molecule, DEANO. The nitrated enkephalin has been examined for its effect on leukocyte functional responses. The data reveal that nitroenkephalin at micromolar concentrations inhibits superoxide anion generation and degranulation of azurophilic granules of human polymorphonuclear cells. Moreover, nitroenkephalin inhibits spontaneous apoptosis of neutrophils, as evaluated by measuring caspase-3 activity. Collectively, our data indicate that the nitrated enkephalin attenuates neutrophil activation and promotes the short-term survival of these cells, suggesting a possible role of the nitrocompound in the efficiency and resolution of inflammatory processes.

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“…Lymphocytederived, endorphin-like molecules could block [3H] dihydromorphine binding to brain tissue and lymphocytes taken from virally induced mice stained positive using a specific antiserum to y-endorphin (56). Macrophages constitutively secrete @-endorphin (57); LPS stimulates production of a-or y-endorphin by leukocytes (58); sheep red blood cells induce opioidlike molecules ( M r = 1300-2000), termed "myelopeptides," by bone marrow cells (59); corticotropin-releasing hormone (CRH) elicits the production of immunoreactive @-endorphin by peripheral blood mononuclear cells (60) and splenic and mesenteric lymph node lymphocytes (6 1); and phytohemagglutinin elicits the production of proenkephalin-derived peptides by lymphocytes (62). Macrophages constitutively secrete @-endorphin (57); LPS stimulates production of a-or y-endorphin by leukocytes (58); sheep red blood cells induce opioidlike molecules ( M r = 1300-2000), termed "myelopeptides," by bone marrow cells (59); corticotropin-releasing hormone (CRH) elicits the production of immunoreactive @-endorphin by peripheral blood mononuclear cells (60) and splenic and mesenteric lymph node lymphocytes (6 1); and phytohemagglutinin elicits the production of proenkephalin-derived peptides by lymphocytes (62).…”

Section: The Production Of Opioid Peptides By Immunocytesmentioning

confidence: 99%

The Role of Endogenous Opioids and Their Receptors in the Immune System

Carr

1991

Experimental Biology and Medicine

104

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Opioid peptides appear to be dynamic signaling molecules that are produced within the immune system and are active regulators of an immune response. Furthermore, the receptors for these peptides occurring on immunocyte membranes share characteristics with neuronal opioid receptors, including molecular size, immunogenicity, and the use of specific intracellular signaling pathways. Recent studies of the interaction of opioids with cytokines have indicated that opioid peptides are intimately involved within the immune system. Specifically, opioids, including 2-n-pentyloxy-2-phenyl-4-methyl-morpholine, naloxone, and beta-endorphin, have been shown to interact with IL-2 receptors (134) and regulate production of IL-1 and IL-2 (48-50, 135). Conversely, IL-1 has been shown to up-regulate opioid peptide binding in brain tissue (136). Furthermore, the induction of IL-1 by opioids has also been identified in the invertebrate Mytilus, indicating the evolutionary conservation of this relationship (137). These results seem to typify the intricate association between the immune and neuroendocrine systems through opioid pathways. It is predicted that future endeavors will use this relationship to diagnose and treat specific diseases that have at their basis neuroendocrine and immunologic imbalances.

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Mitogenic activation of the human lymphocytes induce the release of proenkephalin derived peptides

Cited by 24 publications

References 21 publications

Dual role of osteoblastic proenkephalin derived peptides in skeletal tissues

Dual role of osteoblastic proenkephalin derived peptides in skeletal tissues

Oxidative and nitrative modifications of enkephalins by human neutrophils: effect of nitroenkephalin on leukocyte functional responses

The Role of Endogenous Opioids and Their Receptors in the Immune System

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