scholarly journals Substance P and IL-33 administered together stimulate a marked secretion of IL-1β from human mast cells, inhibited by methoxyluteolin

2018 ◽  
Vol 115 (40) ◽  
pp. E9381-E9390 ◽  
Author(s):  
Alexandra Taracanova ◽  
Irene Tsilioni ◽  
Pio Conti ◽  
Errol R. Norwitz ◽  
Susan E. Leeman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mast Cell ◽  
Mast Cells ◽  
Substance P ◽  
Proinflammatory Cytokine ◽  
Inflammatory Responses ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Cell Secretion ◽  
Active Caspase

Mast cells are critical for allergic and inflammatory responses in which the peptide substance P (SP) and the cytokine IL-33 are involved. SP (0.01–1 μM) administered together with IL-33 (30 ng/mL) to human cultured LAD2 mast cells stimulates a marked increase (P< 0.0001) in secretion of the proinflammatory cytokine IL-1β. Preincubation of LAD2 (30 min) with the SP receptor (NK-1) antagonists L-733,060 (10 μM) or CP-96345 (10 µM) inhibits (P< 0.001) secretion of IL-1β stimulated by either SP (1 μM) or SP together with IL-33 (30 ng/mL). Surprisingly, secretion of IL-1β stimulated by IL-33 is inhibited (P< 0.001) by each NK-1 antagonist. Preincubation with an antibody against the IL-33 receptor ST2 inhibits (P< 0.0001) secretion of IL-1β stimulated either by IL-33 or together with SP. The combination of SP (1 μM) with IL-33 (30 ng/mL) increases IL-1β gene expression by 90-fold in LAD2 cells and by 200-fold in primary cultured mast cells from human umbilical cord blood. The combination of SP and IL-33 increases intracellular levels of IL-1β in LAD2 by 100-fold and gene expression of IL-1β and procaspase-1 by fivefold and pro-IL-1β by twofold. Active caspase-1 is present even in unstimulated cells and is detected extracellularly. Preincubation of LAD2 cells with the natural flavonoid methoxyluteolin (1–100 mM) inhibits (P< 0.0001) secretion and gene expression of IL-1β, procaspase-1, and pro-IL-1β. Mast cell secretion of IL-1β in response to SP and IL-33 reveals targets for the development of antiinflammatory therapies.

scholarly journals Expression of Functional TrkA Receptor Tyrosine Kinase in the HMC-1 Human Mast Cell Line and in Human Mast Cells

Blood ◽  
1997 ◽  
Vol 90 (5) ◽  
pp. 1807-1820 ◽  
Author(s):  
See-Ying Tam ◽  
Mindy Tsai ◽  
Masao Yamaguchi ◽  
Koji Yano ◽  
Joseph H. Butterfield ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tyrosine Kinase ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Human Mast Cell ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Human Mast Cells

Abstract Nerve growth factor (NGF ) can influence mast cell development and function in murine rodents by interacting with its receptors on mast cells. We now report the identification of mRNA transcripts of full-length tyrosine kinase-containing trkA, trkB, and trkC neurotrophin receptor genes in HMC-1 human mast cell leukemia cells. Although HMC-1 cells lacked p75 mRNA, they expressed transcripts for the exon-lacking splice variant of trkA (trkAI), truncated trkB (trkB.T1), and truncated trkC. By flow cytometry, HMC-1 cells exhibited expression of TrkA, TrkB, and TrkC receptor proteins containing full-length tyrosine kinase domains. NGF stimulation of HMC-1 cells induced tyrosine phosphorylation of TrkA protein, increased expression of the early response genes c-fos and NGF1-A, and activation of ERK-mitogen–activated protein (MAP) kinase, results which indicate that TrkA receptors in HMC-1 cells are fully functional. Highly purified populations of human lung mast cells expressed mRNAs for trkA, trkB and trkC, whereas preparations of human umbilical cord blood-derived mast cells expressed mRNAs for trkA and trkC, but not trkB. Moreover, preparations of human umbilical cord blood-derived immature mast cells not only expressed mRNA transcript and protein for TrkA, but exhibited significantly higher numbers of chymase-positive cells after the addition of NGF to their culture medium for 3 weeks. In addition, HMC-1 cells expressed mRNAs for NGF, brain-derived neurotrophic factor (BDNF ), and neurotrophin-3 (NT-3), the cognate ligands for TrkA, TrkB, and TrkC, whereas NGF and BDNF transcripts were detectable in human umbilical cord blood mast cell preparations. Taken together, our findings show that human mast cells express a functional TrkA receptor tyrosine kinase and indicate that NGF may be able to promote certain aspects of mast cell development and/or maturation in humans. Our studies also raise the possibility that human mast cells may represent a potential source for neurotrophins.

Substance P enhances electrical field stimulation-induced mast cell degranulation in rat trachea

1996 ◽  
Vol 270 (6) ◽  
pp. L985-L991 ◽  
Author(s):  
X. Y. Hua ◽  
S. M. Back ◽  
E. K. Tam
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Substance P ◽  
Electrical Field Stimulation ◽  
Mast Cell Degranulation ◽  
Facilitatory Effect ◽  
Neurokinin A ◽  
Field Stimulation ◽  
Cell Secretion ◽  
Electrical Field

We previously demonstrated in an ex vivo rat tracheal model that chymotryptic activity is an index of mast cell degranulation and that substance P (SP) and electrical field stimulation (EFS) synergistically degranulate mucosal and connective tissue mast cells. In the current study, we found that the facilitatory effect of SP was apparent at concentrations as low as 10(-9) M. This effect was mimicked by 10(-7) M neurokinin A or by 10(-6) M capsaicin and was blocked by the NK1 receptor antagonist CP-96,345. SP + EFS-induced mast cell secretion was significantly attenuated by 10(-6) M tetrodotoxin. The response was also attenuated in tracheas from rats in which sensory nerves had been depleted by systemic pretreatment with capsaicin or in which sympathetic nerves had been depleted by systemic pretreatment with 6-hydroxy-dopamine. Atropine (10(-6) M) or indomethacin (10(-5) M) also attenuated SP + EFS-induced mast cell secretion. Our findings suggest the importance of a sensitizing rather than a direct stimulating effect of SP on mast cell degranulation. SP may increase the sensitivity of mast cells to EFS-discharged mediators or facilitate the release of mast cell-stimulating mediators from autonomic nerves.

scholarly journals Neuropeptide Substance P induces mRNA expression and secretion of CXCL8 chemokine, and HDC in human umbilical cord blood mast cells

2008 ◽  
Vol 31 (6) ◽  
pp. 362 ◽  
Author(s):  
M L Castellani ◽  
C Ciampoli ◽  
M Felaco ◽  
S Tetè ◽  
C M Conti ◽  
...  
Keyword(s):  
Mast Cells ◽  
Substance P ◽  
Cord Blood ◽  
Histidine Decarboxylase ◽  
Calcium Ionophore ◽  
Free Calcium ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Ionophore A23187 ◽  
Human Cord Blood

Purpose: Mast cells play an important role in innate and acquired immunity and are thought to be the cellular origin of most proteases and cytokines. Substance P (SP) and its receptor, NK-1R, play critical roles in immune regulation in human and animal models of inflammation. Methods: We used mature human cord blood mast cells (HCBMC) differentiated from cord blood CD34+ precursor activated with SP in culture. Results: Our data indicate that Substance P strongly activates mature HCBMC in releasing CXCL8 expression and secretion (Control: 1.200 ± 1.0; SP: 4.10 ± 0.90; P < 0.01). Moreover, in a RT-PCR, HCBMC expressed CXCL8 mRNA after Substance P activation. Since calcium ionophore A23187 is a pharmacological activator that raises cytosolic free calcium ion concentraion and stimulates mast cells in the production and secretion of proinflammatory compounds, it was used as positive control. In addition, we found that HCBMCs generate the transcription of histidine decarboxylase (HDC), the enzyme responsible for the generation of histamine from histidine, after SP treatment. Since CXCL8 is a member of the CXC chemokine subfamily with potent chemotactic activity and is a primary inflammatory cytokine we conclude that our results, obtained from HCBMC cultures, a good and valid model in vitro, support the concept that the neurogenic system modulates inflammatory events by Substance P-mediated HCBMC chemokine CXCL8 release. Conclusion: The expression, synthesis and release of CXCL8 suggest an increase of inflammatory process in vivo mediated by the recruitment and infiltration of inflammatory cells in inflamed tissues.

scholarly journals Regulation of corticotropin-releasing hormone receptor-2 expression in human cord blood-derived cultured mast cells

2005 ◽  
Vol 35 (3) ◽  
pp. R1-R8 ◽  
Author(s):  
Nikoletta G Papadopoulou ◽  
Lauren Oleson ◽  
Duraisamy Kempuraj ◽  
Jill Donelan ◽  
Curtis L Cetrulo ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cord Blood ◽  
Cell Activation ◽  
Inflammatory Diseases ◽  
Mast Cell Activation ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone

Corticotropin-releasing hormone (CRH) is secreted under stress and regulates the hypothalamic-pituitary-adrenal (HPA) axis; it is also secreted outside the brain where it exerts proinflammatory effects, possibly through mast cell activation. Mast cells are necessary for allergic reactions, but are increasingly implicated in acquired immunity and inflammatory diseases worsened by stress. Acute stress and intradermal CRH induced murine skin mast cell activation and increased vascular permeability that was absent in W/Wv mast cell deficient mice. The presence of functional CRH receptors (CRH-R) was recently reported on human mast cells. Here, we studied the expression of CRH-R1 and CRH-R2 by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescent immunocytochemistry in human umbilical cord blood-derived cultured mast cells (hCBMCs) treated with Interleukin (IL)-1, IL-4 or lipopolysaccharide (LPS). Ten week-old hCBMCs cultured in the presence of Stem cell factor (SCF) and IL-6 were positive for both CRH-R1 and CRH-R2. However, the expression of only CRH-R2 mRNA and protein was induced by priming hCBMCs with IL-4 for the last three weeks of culture. Further analysis of the CR-H R2 mRNA expression showed that addition of IL-1 or LPS for 6 h increased only CRH-R2 gene expression. CRH had negligible effect on IL-6 secretion from non-primed hCBMCs, but induced release from IL-4 primed cells. Interestingly, LPS alone increased IL-6 release in non-primed cells, but lost this effect in primed cells. These results further implicate mast cells and CRH in either initiating or potentiating inflammatory diseases, especially those affected by stress.

Mast cell-nerve fiber interaction: Ultrastructural studies

1990 ◽  
Vol 48 (3) ◽  
pp. 428-429
Author(s):  
E.Y. Chi ◽  
M.L. Su ◽  
Y.T. Tien ◽  
W.R. Henderson
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Substance P ◽  
Nerve Fiber ◽  
Sensory Nerves ◽  
Ultrastructural Studies ◽  
Morphological Studies ◽  
Granulocyte Infiltration ◽  
Intracutaneous Injection ◽  
Recent Attention

Recent attention has been directed to the interaction of the nerve and immune systems. The neuropeptide substance P, a tachykinnin which is a neurotransmitter in the central and peripheral nervous systems produces tissue swelling, augemntation of intersitial fibrin deposition and leukocyte infiltration after intracutaneous injection. There is a direct correlation reported between the extent of mast cell degranulation at the sites of injection and the tissue swelling or granulocyte infiltration. It has previously been demonstrated that antidromic electrical stimulation of sensory nerves induces degranulation of cutaneous mast cells, cutaneous vasodilation and augmented vascular permeability. Morphological studies have documented a close anatiomical association between mast cells and nonmyelinated nerves, that contain substance P and other neuropeptides. However, the presence of mast cells within nerve fasicles has not been previously examined ultrastructurally. In this study, we examined ultrastructurally the distribution of mast cells in the nerve fiber bundles located in the muscular connective tissue of rat tongues (n=20).

Mast cell heterogeneity

1984 ◽  
Vol 62 (6) ◽  
pp. 734-737 ◽  
Author(s):  
F. Shanahan ◽  
J. A. Denburg ◽  
J. Bienenstock ◽  
A. D. Befus
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Regulatory Peptides ◽  
Cell Heterogeneity ◽  
Cell Secretion ◽  
Biochemical Basis ◽  
Mucosal Mast Cells ◽  
Mast Cell Heterogeneity

Increasing evidence for the existence of inter- and intra-species mast cell heterogeneity has expanded the potential biological role of this cell. Early studies suggesting that mast cells at mucosal sites differ morphologically and histochemically from connective tissue mast cells have been confirmed using isolated intestinal mucosal mast cells in the rat and more recently in man. These studies also established that mucosal mast cells are functionally distinct from connective tissue mast cells. Thus, mucosal and connective tissue mast cells differ in their responsiveness to a variety of mast cell secretagogues and antiallergic agents. Speculation about the therapeutic use of antiallergic drugs in disorders involving intestinal mast cells cannot, therefore, be based on extrapolation from studies of their effects on mast cells from other sites. Regulatory mechanisms for mast cell secretion may also be heterogeneous since mucosal mast cells differ from connective tissue mast cells in their response to a variety of physiologically occurring regulatory peptides. The development of techniques to purify isolated mast cell sub-populations will facilitate future analysis of the biochemical basis of the functional heterogeneity of mast cells.

scholarly journals Mast cell growth factor (c-kit ligand) supports the growth of human multipotential progenitor cells with a high replating potential

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2216-2221 ◽  
Author(s):  
CE Carow ◽  
G Hangoc ◽  
SH Cooper ◽  
DE Williams ◽  
HE Broxmeyer
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Cord Blood ◽  
Primary Cultures ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Factor C ◽  
Mast Cell Growth Factor

Abstract The replating capability of human multipotential (colony-forming unit- granulocyte-erythrocyte-macrophage-megakaryocyte [CFU-GEMM]) and erythroid (burst-forming unit-erythroid [BFU-E]) progenitors was assessed in vitro as a potential measure of self-renewal using purified, recombinant (r) human (hu) or murine (mu) mast cell growth factor (MGF), a ligand for the c-kit proto-oncogene receptor. Primary cultures of human umbilical cord blood or adult human bone marrow cells were initiated in methylcellulose with erythropoietin (Epo) alone or in combination with rhu interleukin-3 (IL-3) or MGF. Individual day 14 to 18 CFU-GEMM or BFU-E colonies were removed from primary cultures and reseeded into secondary methylcellulose cultures containing a combination of Epo, MGF, and rhu granulocyte-macrophage colony- stimulating factor (GM-CSF). The data showed a high replating efficiency of cord blood and bone marrow CFU-GEMM in response to Epo + MGF in terms of the percentage of colonies that could be replated and the number of secondary colonies formed per replated primary colony. The average number of hematopoietic colonies and clusters apparent from replated cultures of cord blood or bone marrow CFU-GEMM stimulated by Epo + MGF was greater than with Epo + rhuIL-3 or Epo alone. Replated cord blood CFU-GEMM gave rise to CFU-GEMM, BFU-E, and GM colony-forming units (CFU-GM) in secondary cultures. Replated bone marrow CFU-GEMM gave rise mainly to CFU-GM in secondary cultures. A more limited capacity for replating of cord blood and bone marrow BFU-E was observed. These studies show that CFU-GEMM responding to MGF have an enhanced replating potential, which may be promoted by MGF. These studies also support the concept that MGF acts on more primitive progenitors than IL-3.

scholarly journals Mast Cell Responses to Viruses and Pathogen Products

2019 ◽  
Vol 20 (17) ◽  
pp. 4241 ◽  
Author(s):  
Jean S. Marshall ◽  
Liliana Portales-Cervantes ◽  
Edwin Leong
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immune Responses ◽  
Viral Infection ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Local Source ◽  
Type I ◽  
Viral Challenge ◽  
Cell Responses

Mast cells are well accepted as important sentinel cells for host defence against selected pathogens. Their location at mucosal surfaces and ability to mobilize multiple aspects of early immune responses makes them critical contributors to effective immunity in several experimental settings. However, the interactions of mast cells with viruses and pathogen products are complex and can have both detrimental and positive impacts. There is substantial evidence for mast cell mobilization and activation of effector cells and mobilization of dendritic cells following viral challenge. These cells are a major and under-appreciated local source of type I and III interferons following viral challenge. However, mast cells have also been implicated in inappropriate inflammatory responses, long term fibrosis, and vascular leakage associated with viral infections. Progress in combating infection and boosting effective immunity requires a better understanding of mast cell responses to viral infection and the pathogen products and receptors we can employ to modify such responses. In this review, we outline some of the key known responses of mast cells to viral infection and their major responses to pathogen products. We have placed an emphasis on data obtained from human mast cells and aim to provide a framework for considering the complex interactions between mast cells and pathogens with a view to exploiting this knowledge therapeutically. Long-lived resident mast cells and their responses to viruses and pathogen products provide excellent opportunities to modify local immune responses that remain to be fully exploited in cancer immunotherapy, vaccination, and treatment of infectious diseases.

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