Differential release of serotonin and histamine from mast cells

Theoharides, Theoharis C.; Bondy, Philip K.; Tsakalos, Nikolaos D.; Askenase, Philip W.

doi:10.1038/297229a0

Cited by 221 publications

(123 citation statements)

References 26 publications

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“…The very first report of differential secretion involved the release of serotonin without histamine in the absence of degranulation from rat peritoneal mast cells (44). However, this differential release of serotonin involved vesicles containing high affinity serotonin binding proteins (45) that appeared to bud off from secretory granules (46).…”

Section: Discussionmentioning

confidence: 99%

IL-1 Induces Vesicular Secretion of IL-6 without Degranulation from Human Mast Cells

Kandere‐Grzybowska

Létourneau

Kempuraj

et al. 2003

The Journal of Immunology

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205

142

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FcεRI cross-linkage in mast cells results in release of granule-associated mediators, such as histamine and proteases, as well as the production of numerous cytokines, including IL-6. Mast cells have been increasingly implicated in inflammatory processes where explosive degranulation is not commonly observed. Here, we show that IL-1 stimulates secretion of IL-6 without release of the granule-associated protease tryptase in normal human umbilical cord blood-derived mast cells (hCBMCs). IL-6 secretion stimulated by IL-1 in hCBMCs is potentiated by priming with IL-4 and reflects the higher levels of IL-6 secreted from human leukemic mast cell line (HMC-1). Stimulating HMC-1 cells by both IL-1 and TNF-α results in synergistic secretion of IL-6. IL-6 is de novo synthesized, as its secretion is blocked by inhibitors of transcription or protein synthesis. IL-1 does not increase intracellular calcium ion levels in either hCBMCs or HMC-1 cells, and IL-6 stimulation proceeds in the absence of extracellular calcium ions. Ultrastructural Immunogold localization shows that IL-6 is excluded from the secretory granules and is compartmentalized in 40- to 80-nm vesicular structures. Selective secretion of IL-6 from mast cells appears distinct from degranulation and may contribute to the development of inflammation, where the importance of IL-6 has been recognized.

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Section: Discussionmentioning

confidence: 99%

IL-1 Induces Vesicular Secretion of IL-6 without Degranulation from Human Mast Cells

Kandere‐Grzybowska

Létourneau

Kempuraj

et al. 2003

The Journal of Immunology

Self Cite

205

142

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“…Mast cells have the ability to secrete individual granules (in contrast to indiscriminate degranulation in an anaphylactic reaction) or distinct mediators selectively. 96,97 For instance, acidity inhibits allergic degranulation but promotes IL-4 production. IL-6 can be secreted without histamine in vitro; and murine mast cells can secrete VEGF without parallel release of serotonin.…”

Section: 94mentioning

confidence: 99%

Mast cells and cutaneous malignancies

Ch’ng

Wallis

Yuan³

et al. 2006

Modern Pathology

165

163

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This paper reviews the role of mast cells in the development and progression of basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Mast cells accumulate around cutaneous malignancies. Current evidence suggests that mast cells contribute to the tumorigenesis of cutaneous malignancies through four mechanisms. (1) Immunosuppression: Ultraviolet-B radiation, the most important initiator of cutaneous malignancies, activates mast cells. Upon irradiation of the skin, trans-urocanic acid in the epidermis isomerizes to cis-urocanic acid, which stimulates neuropeptide release from neural c-fibers. These neuropeptides in turn trigger histamine secretion from mast cells, leading to suppression of the cellular immune system. (2) Angiogenesis: Mast cells are the major source of vascular endothelial growth factor in basal cell carcinoma and malignant melanoma. Vascular endothelial growth factor is one of the most potent angiogenic factors, which also induces leakage of other angiogenic factors across the endothelial cell wall into the matrix. Mast cell proteases reorganize the stroma to facilitate endothelial cell migration. As well, heparin, the dominant mast cell proteoglycan, assists in blood-borne metastasis. (3) Degradation of extracellular matrix: Through its own proteases, and indirectly via interaction with other cells, mast cells participate in degradation of the matrix, which is required for tumor spread. (4) Mitogenesis: Mast cell mediators including fibroblast growth factor-2 and interleukin-8 are mitogenic to melanoma cells. Current evidence supports an accessory role for mast cells in the development and progression of cutaneous malignancies. Emerging data, however, also suggest that mast cells might, in fact, have opposing roles in tumor biology, and the microenvironment could polarize mast cells to possess either promoting or inhibitory effects on tumors.

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“…Finally, an increase in mast cells does not necessarily refl ect a deleterious infl ammatory process. Mast cells can secrete selectively ( 19 ) and can secrete growth factors involved in tissue healing ( 3 ).…”

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confidence: 99%

Editorial: Irritable Bowel Syndrome and the Elusive Mast Cells

Theoharides¹,

Asadi²,

Chen³

et al. 2012

American Journal of Gastroenterology

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Irritable bowel syndrome (IBS) is the most common condition seen by gastroenterologists. It presents with alternating symptoms of bowel dysfunction that often worsens with stress. The cause of these symptoms eludes investigators and many attempts have been made to discover an underlying pathology. This is a daunting task since symptoms come and go, and change characteristics. Furthermore, the pathology of IBS is unlikely to be identical in all patients. In addition, all symptoms and all features studied thus far have a strong overlap with healthy volunteers. Elsewhere in this issue, Braak et al. report a well-designed clinical investigation in patients with IBS and come to the conclusion that IBS is not characterized by mast cell or other immune cell proliferation, but by immune dysregulation in the colon. Is this the fi nal answer? Am J Gastroenterol 2012; 107:727 -729; doi: 10.1038/ajg.2012 Irritable bowel syndrome (IBS) is a common functional disorder in the West ( 1 ) and in Asia ( 2 ), which is characterized clinically as abdominal discomfort or pain with alternating constipation and diarrhea. Mechanistic pathways to symptom generation are unclear, although dysfunction of brain-gut communication, gut motility, visceral perception, neuroimmune responses, infl ammation, and mucosal integrity, as well as the psychosocial status might be involved ( 3 ). Th e mucosa contains endings of the enteric sensory nerves; these aff erent nerves can modify motility and pain perception. Th erefore, immune cell infi ltration assessed in mucosal biopsies may provide critical information on the mechanisms of symptom generation. Both intestinal ( 4 ) and colonic ( 5,6 ) biopsies have been investigated. Mast cells have received particular attention because its secretory products, such as histamine, prostaglandins, and proteinases, are capable of sensorimotor dysfunction. IBS appears to worsen with stress and the important information might be obtained from relationships between stress, corticotropin-releasing hormone (CRH) and symptoms ( 7 ). CRH signaling pathways have been shown to have an important role in stress-related alterations of gut function related to intestinal symptoms ( 7 ). Braak et al. ( 8 ) have attempted to clarify IBS pathophysiology using these strategies.Mast cells are well known to modulate gastrointestinal pathophysiology and are considered to be involved in IBS ( 9 ). Increased numbers of mast cells have been reported in the terminal ileum in patients with IBS, although there was lack of correlation with diarrhea-predominant IBS symptoms ( 4 ). Braak et al. ( 8 ) conclude that the number of mast cells, macrophages (CD68), T cells (CD3 and CD8), and λ FLC-positive mast cells is decreased in IBS patients compared with healthy volunteers. As a general statement, this needs clarifi cation. Th ey note the decrease in the descending colon, but no change was seen in the ascending colon and immune cell numbers in the small intestine were not measured. Furthermore, mast cells in the gut musculature ( ...

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Differential release of serotonin and histamine from mast cells

Cited by 221 publications

References 26 publications

IL-1 Induces Vesicular Secretion of IL-6 without Degranulation from Human Mast Cells

IL-1 Induces Vesicular Secretion of IL-6 without Degranulation from Human Mast Cells

Mast cells and cutaneous malignancies

Editorial: Irritable Bowel Syndrome and the Elusive Mast Cells

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