Ultrastructural evidence for mast cell-macrophage interrelationships in the dura mater of the rat: Infrequent mast cell-nerve associations

Author(s):  
Ruth V.W. Dimlich

Mast cells in the dura mater of the rat may play a role in cerebral pathologies including neurogenic inflammation (vasodilation; plasma extravasation) and headache pain . As has been suggested for other tissues, dural mast cells may exhibit a close spatial relationship to nerves. There has been no detailed ultrastructural description of mast cells in this tissue; therefore, the goals of this study were to provide this analysis and to determine the spatial relationship of mast cells to nerves and other components of the dura mater in the rat.Four adult anesthetized male Wistar rats (290-400 g) were fixed by perfusion through the heart with 2% glutaraldehyde and 2.8% paraformaldehyde in a potassium phosphate buffer (pH 7.4) for 30 min. The head of each rat was removed and stored in fixative for a minimum of 24 h at which time the dural coverings were removed and dissected into samples that included the middle meningeal vasculature. Samples were routinely processed and flat embedded in LX 112. Thick (1 um) sections from a minimum of 3 blocks per rat were stained with toluidine blue (0.5% aqueous).

Cephalalgia ◽  
2012 ◽  
Vol 32 (4) ◽  
pp. 337-345 ◽  
Author(s):  
Michael Baun ◽  
Martin Holst Friborg Pedersen ◽  
Jes Olesen ◽  
Inger Jansen-Olesen

Background: Pituitary adenylate cyclase activating peptide-38 (PACAP-38) has been shown to induce migraine in migraineurs, whereas the related peptide vasoactive intestinal peptide (VIP) does not. In the present study we examine the hypothesis that PACAP-38 and its truncated version PACAP-27 but not VIP cause degranulation of mast cells in peritoneum and in dura mater. Methods: The degranulatory effects of PACAP-38, PACAP-27 and VIP were investigated by measuring the amount of N-acetyl-β-hexosaminidase released from isolated peritoneal mast cells and from dura mater attached to the skull of the rat in vitro. In peritoneal mast cells N-truncated fragments of PACAP-38 (PACAP(6–38), PACAP(16–38) and PACAP(28–38)) were also studied. To investigate transduction pathways involved in mast cell degranulation induced by PACAP-38, PACAP-27 and VIP, the phospholipase C inhibitor U-73122 and the adenylate cyclase inhibitor SQ 22536 were used. Results: The peptides induced degranulation of isolated peritoneal mast cells of the rat with the following order of potency: PACAP-38 = PACAP(6–38) = PACAP(16–38) » PACAP-27 = VIP = PACAP(28–38). In the dura mater we found that 10−5 M PACAP-38 was significantly more potent in inducing mast cell degranulation than the same concentration of PACAP-27 or VIP. Inhibition of intracellular mechanisms demonstrated that PACAP-38-induced degranulation is mediated by the phospholipase C pathway. Selective blockade of the PAC1 receptor did not attenuate degranulation. Conclusion: These findings correlate with clinical studies and support the hypothesis that mast cell degranulation is involved in PACAP-induced migraine. PACAP-38 has a much stronger degranulatory effect on rat peritoneal and dural mast cells than VIP and PACAP-27. The difference in potency between PACAP-38- and PACAP-27/VIP-induced peritoneal mast cell degranulation is probably not related to the PAC1 receptor but is caused by a difference in efficacy on phospholipase C.


2005 ◽  
Vol 288 (2) ◽  
pp. R491-R500 ◽  
Author(s):  
Michael R. D'Andrea ◽  
Marcia R. Saban ◽  
Norma P. Gerard ◽  
Barry K. Wershil ◽  
Ricardo Saban

A spatial association between mast cells and nerves has been described in both the gastrointestinal and genitourinary tracts. However, the factors that influence the anatomic relationship between mast cells and nerves have not been completely defined. It has been suggested that the high-affinity receptor for substance P [neurokinin-1 (NK1)] might modulate this interaction. We therefore assessed mast cell-nerve relationships in tissues isolated from wild-type and NK1 receptor knockout (NK1−/−) mice. We now report that, in the complete absence of NK1 receptor expression, there is a significant increase in the number of mast cells without a change in the anatomic relationship between mast cell and nerves in stomach and bladder tissues at the light microscopic level. We next determined whether transplanted mast cells would maintain their spatial distribution, number, and contact with nerve elements. For this purpose, mast cell-deficient Kit W /Kit W−v mice were reconstituted with wild-type or NK1−/− bone marrow. No differences in mast cell-nerve contact were observed. These results suggest that NK1 receptor expression is important in the regulation of the number of mast cells but is not important in the interaction between mast cells and nerves. Furthermore, the interaction between mast cells and nerves is not mediated through NK1 receptor expression on the mast cell. Further studies are needed to determine the molecular pathway involved in mast cell migration and interaction with nerve elements, but the model of reconstitution of Kit W /Kit W−v mice with mast cells derived from different genetically engineered mice is a useful approach to further explore these mechanisms.


Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 993-998 ◽  
Author(s):  
T Jippo ◽  
H Mizuno ◽  
Z Xu ◽  
S Nomura ◽  
M Yamamoto ◽  
...  

Although GATA-binding transcription factors (GATA-1 and GATA-2) are strongly expressed in cultured mast cells (CMCs), their expression in mast cells within tissues has not been reported. We examined the expression of GATA-1 and GATA-2 in skin tissues of mice using Northern blot analysis and in situ hybridization. mRNA for GATA-2 but not for GATA-1 was expressed in skin mast cells of WB-+/+ embryos between days 15 and 17 postcoitum (pc). The expression was downregulated on and after day 18 pc. Skin mast cells did not express GATA-2 after birth either. When the number of skin mast cells was compared with the number of GATA-2 mRNA-expressing cells, GATA-2 mRNA appeared to be expressed by mast cells only when the number was increasing. When the mRNA expression of high-affinity IgE receptor beta-subunit and mast cell carboxypeptidase A was used as differentiation markers, the expression of these mRNAs continued even after the downregulation of GATA-2 expression. To clarify the relationship of the proliferation and GATA-2 expression, proliferating CMCs derived from WBB6F1-+/+ mice were transplanted into the peritoneal cavity of mast cell-deficient WBB6F1- W/Wv mice. The CMCs stopped both the proliferation and GATA-2 expression after the transplantation, suggesting the association of these two parameters in mast cells within tissues of mice.


2017 ◽  
Vol 104 (1) ◽  
pp. 15-24 ◽  
Author(s):  
E Kilinc ◽  
Y Dagistan ◽  
B Kotan ◽  
A Cetinkaya

In this study, we aimed to investigate the effects of Nigella sativa seeds and certain species of fungi extracts on the number and degranulation states of dural mast cells in rats. Rats were fed ad libitum with normal tap water or tap water with extract of N. sativa seed, Ramaria condensata, Lactarius salmonicolor, Lactarius piperatus, and Tricholoma terreum for 3 days. Mast cells in dura mater were counted and evaluated in terms of granulation and degranulation states. Compound 48/80, a mast cell degranulating agent, and T. terreum significantly increased the percent of degranulated mast cells in dura mater, respectively (p < 0.01 and p < 0.05). Moreover, T. terreum causes a significant increase in the total number of mast cells (p < 0.05). N. sativa significantly inhibited mast cell degranulation induced by both the compound 48/80 and T. terreum (p < 0.05), and significantly decreased the mast cell numbers increased by T. terreum (p < 0.05). Our results suggested that T. terreum following ingestion can contribute to headaches like migraine via dural mast cell degranulation and N. sativa may be able to exert analgesic and anti-inflammatory effects by stabilizing dural mast cells. However, investigation is needed to determine the ingredients of N. sativa that may be responsible for these beneficial effects.


1989 ◽  
Vol 477 (1-2) ◽  
pp. 157-165 ◽  
Author(s):  
Stephen Markowitz ◽  
Kiyoshi Saito ◽  
Maria Gabriella Buzzi ◽  
Michael A. Moskowitz

2014 ◽  
Vol 4 (8) ◽  
pp. 658-662 ◽  
Author(s):  
N Mainali ◽  
AK Sihna ◽  
P Upadhyaya ◽  
D Upreti

Background: Mast cells are heterogeneous group of immune cells involved in multiple biological events. The significance of mast cells in uterine tumor surveillance has been studied with conflicting results. The presence of mast cell in tumor has been described as evidence of a host immunologic anti tumor response and if they are abundant the prognosis is good. However in other studies, with the help of different granules of mast cell, it is said to be very closely related with angiogenesis and tumor invasion. The study aims to analyze the histomorphologic changes with special reference to mast cells in different neoplastic and non neoplastic disease of uterine cervix, and also the relationship of the mast cell population with degree of anaplasia and mitotic figures.Materials and methods: Cervical biopsies received in the department of Pathology for HPE were stained with H& E stain and toludine blue for the identification of mast cellResult: Out of a total of 100 cases, 82 were non neoplastic cases with the mean mast cell count of 83.73 and mean age of patient being 44.30 year. Eighteen neoplastic cases were included which had mean mast cell count of 13.5 and mean age of 49.5 year.Conclusion: Mast cell was found to be highest in non Neoplastic lesion with increase count in polypoidal cervicitis. There was a statistical significance variation between mast cell count in neoplastic and non Neoplastic disease of the cervix. However,role of age in mast cell count was least significant.DOI: http://dx.doi.org/10.3126/jpn.v4i8.11594 Journal of Pathology of Nepal; Vol.4,No. 8 (2014) 658-662


2005 ◽  
Vol 202 (2) ◽  
pp. 217-224 ◽  
Author(s):  
Maiko Moriyama ◽  
Takahiro Sato ◽  
Hiromasa Inoue ◽  
Satoru Fukuyama ◽  
Hitoshi Teranishi ◽  
...  

Neuromedin U (NMU) is a neuropeptide that is expressed in the gastrointestinal tract and central nervous system. NMU interacts with two G protein–coupled receptors, NMU-R1 and NMU-R2. Whereas NMU-R2 localizes predominantly to nerve cells, NMU-R1 is expressed in peripheral tissues including lymphocytes and monocytes, suggesting a role of NMU in immunoregulation. However, the functions of NMU in peripheral tissues have not been clarified. In this study, using NMU-deficient mice, we first demonstrated that NMU plays an important role in mast cell-mediated inflammation. Complete Freund's adjuvant-induced mast cell degranulation as well as edema and neutrophil infiltration, which occurred weakly in mast cell–deficient WBB6F1-W/Wv mice, did not occur in NMU-deficient mice. Moreover, intraplantar injection of NMU into paws induced early inflammatory responses such as mast cell degranulation, vasodilation, and plasma extravasation in WT mice but not in WBB6F1-W/Wv mice. NMU-R1 was highly expressed in primary mast cells, and NMU induced Ca2+ mobilization and degranulation in peritoneal mast cells. These data indicate that NMU promotes mast cell–mediated inflammation; therefore, NMU receptor antagonists could be a novel target for pharmacological inhibition of mast cell–mediated inflammatory diseases.


PEDIATRICS ◽  
1958 ◽  
Vol 21 (5) ◽  
pp. 805-812
Author(s):  
Lytt I. Gardner ◽  
Artelissa A. Tice

Tissue from the liver and spleen of a child with urticaria pigmentosa have been analyzed chemically for histamine and related compounds. Both tissues were infiltrated with mast cells. Trichloroacetic acid extracts of tissue from the liver of the child with urticaria pigmentosa were chromatogaphed on paper. Histamine was demonstrated as a double-spot formation similar to that described by previous workers who have chromatographed histamine-rich tissues. The histamine was present in the tissue in several hundred times the normal concentration, and exceeded the values for human tissue reported in the available literature. No serotonin could be detected in these human mast cells, a finding in contrast with previous reports of increased serotonin content in rodent mast cells, and in agreement with the findings of Sjoerdsma et al. who could find no serotonin in skin from a patient with urticaria pigmentosa. Our studies suggest that the decarboxylation of 5-hydroxytryptophan to serotonin does not take place in the human mast cell. Instead the accumulation of compounds such as 5-hydroxytryptophan, kynurenine or hydroxylated kynurenine may take place. There was no increase in xanthine oxidase activity. Acetone extracts of tissue from the liver were made and the residues chromatographed. In addition to histamine, there were noted three substances of unknown structure resembling tryptophane and/or its metabolites. Chemical evidence suggesting the presence of large amounts of a substance resembling mucoitin sulfuric acid (? heparin) in this tissue was obtained. The possible relationship of such compounds to the biochemical error in urticaria pigmentosa is briefly considered. There are at present no data to indicate whether the enzymatic defect is primary to the intermediary catabolism of histamine or of heparin.


1989 ◽  
Vol 170 (1) ◽  
pp. 245-257 ◽  
Author(s):  
P R Burd ◽  
H W Rogers ◽  
J R Gordon ◽  
C A Martin ◽  
S Jayaraman ◽  
...  

In response to IgE and specific multivalent antigen, mast cell lines (both growth factor-dependent and -independent) induce the transcription and/or secretion of a number of cytokines having a wide spectrum of activities. We have identified IL-1, IL-3, IL-5, IL-6, IFN-gamma, GM-CSF, JE, MIP1 alpha, MIP1 beta, and TCA3 RNA in at least two of four mast cell clones. The production of these products (except JE) is activation-associated and can be induced by IgE plus antigen. In selected instances cytokine expression can also be induced by activation with Con A or phorbol ester plus ionophore, albeit to levels less than those observed with IgE plus antigen. In addition, long-term mast cell clones and primary cultures of bone marrow-derived mast cells specifically release IL-1, IL-4, and/or IL-6 bioactivity after activation. These findings suggest that in addition to their inflammatory effector function mast cells may serve as a source of growth and regulatory factors. The relationship of mast cells to cells of the T lymphocyte lineage is discussed.


2021 ◽  
Author(s):  
Raisa Ferreira Costa ◽  
Emanuela Paz Rosas ◽  
Daniella Araújo de Oliveira ◽  
Marcelo Moraes Valença

Introduction: Capsaicin is able to induce mast cell degranulation, an event probably related to the pathophysiology of a migraine attack. Objectives: The present review study aimed to address the mechanisms of action of capsaicin and other chemical inducers in mast cell degranulation and an interaction of nerves and events that happen in the dura mater with the activation of mast cells. Design: A survey was carried out in the literature, from 1980 to 2019, in different databases (SciELO, U.S. National Library of Medicine and the National Institutes Health (PubMed) and Web of Science) using the following terms: capsaicin, mast cell and dura mater. Methods: 36 articles were selected for this review. The inclusion criteria were experimental model studies in rats that described the mechanisms of action of chemical inducers, including capsaicin. Results: Studies indicate that the main mechanisms of action of capsaicin are chemical induction through the activation of TRPV1 channels, allowing calcium influx into neurons in the trigeminal ganglion of the dura mater, activating mast cell degranulation, releasing pro-inflammatory (e.g., histamine, oxide nitric) and vasoactive (e.g., CGRP and substance P) substances. Conclusion: Therefore, the use of capsaicin may be a tool to be used in na animal model to better understand the pathophysiology of migraine.


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