scholarly journals XANTATINA INHIBE LA ACTIVACIÓN DE MASTOCITOS INDUCIDA POR NEUROPÉPTIDOS PRO-INFLAMATORIOS

2016 ◽  
Vol 2 (1) ◽  
pp. 16-24
Author(s):  
Patricia M. Vargas ◽  
Elia Martino ◽  
Teresa H. Fogal ◽  
Carlos E. Tonn ◽  
Alicia B. Penissi
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Substance P ◽  
Cell Activation ◽  
Neurogenic Inflammation ◽  
Light And Electron Microscopy ◽  
Serotonin Release ◽  
Mast Cell Activation ◽  
Morphological Studies ◽  
Peritoneal Mast Cells

Los mastocitos son células del tejido conectivo que participan en la génesis y modulación de las respuestas inflamatorias. Previamente hemos demos-trado que xanthatina (xanthanólido sesquiterpeno aislado de Xanthium cavanillesii Schouw) inhibe la activación de mastocitos inducida por secretagogos experimentales. Sin embargo, se desconoce su efecto sobre la activación de mastocitos inducida por estímulos fisiopatológicos. Estos estímulos incluyen, entre otros, los neuropéptidos pro-inflamatorios sustancia P y neurotensina, responsables de una de las principales vías de inflamación neurogénica. El objetivo del presente trabajo fue estudiar el efecto de xanthatina sobre la activación de mastocitos inducida por sustancia P y neurotensina. Mastocitos peritoneales de rata se incubaron con: 1) PBS (basal); 2) sustancia P (100 µm); 3) neurotensina (50 µm); 4) xanthatina (8-320 µm)+sustancia P; 5) xanthatina (8-320 µm)+neurotensina. Se llevaron a cabo los siguientes estudios: análisis dosis-respuesta de la liberación de serotonina inducida por neuropéptidos proinflamatorios, vitalidad celular, morfología mastocitaria por microscopía óptica y electrónica, análisis de estabilidad de xanthatina por cromatografía en capa fina. Los ensayos de liberación de serotonina y los estudios morfológicos mostraron la efectividad de xanthatina para estabilizar mastocitos. El presente estudio provee la primer evidencia a favor de la hipótesis de que xanthatina inhibe la liberación de serotonina inducida por sustancia P y neurotensina a partir de mastocitos peritoneales. Este sesquiterpeno podría representar una nueva alternativa fármacológica en la regulación de la activación mastocitaria para el tratamiento de las inflamaciones neurogénicas. Mast cells are connective tissue cells involved in the genesis and modulation of inflammatory responses. We have previously shown that xanthatin (xanthanolide sesquiterpene isolated from Xanthium cavanillesii Schouw) inhibits mast cell activation induced by experimental secretagogues. However, the effect of xanthatin on mast cell activation induced by pathophysiological stimuli remains unknown. These stimuli include, among others, the pro-inflammatory neuropeptide substance P and neurotensin, responsible for one of the main pathways of neurogenic inflammation. The present study was designed to examine the effects of xanthatin on mast cell activation induced by pro-inflammatory peptides, such as substance P and neurotensin. Rat peritoneal mast cells were incubated with: 1) PBS (basal); 2) substance P (100 µm); 3) neurotensin (50 µm); 4) xanthatin (8-320 µm)+substance P; 5) xanthatin (8-320 µm)+neurotensin. Concentration-response studies of mast cell serotonin release evoked by pro-inflammatory neuropeptides, evaluation of mast cell viability and morphology by light and electron microscopy, and drug stability analysis by thin layer chromatography were performed. Serotonin release studies, carried out together with morphological studies, showed the effectiveness of xanthatin to stabilize mast cells. The present study provides the first strong evidence in favour of the hypothesis that xanthatin inhibits substance P - and neurotensin-induced serotonin release from peritoneal mast cells. Our findings may provide an insight into the design of novel pharmacological agents which may be used to regulate the mast cell response in neurogenic inflammation.

Characteristics and Potential Biomarkers for Chronic Pain in Patients with Sickle Cell Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 986-986 ◽  
Author(s):  
Nina Kuei ◽  
Niren Patel ◽  
Hongyan Xu ◽  
Leigh Wells ◽  
Latanya Bowman ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Mast Cell ◽  
Sickle Cell Disease ◽  
Substance P ◽  
Cell Activation ◽  
Neurogenic Inflammation ◽  
Mast Cell Activation ◽  
Cell Disease ◽  
Opioid Use ◽  
Pressure Pain

Abstract Vaso-occlusive episodes (VOE) or pain crises are a hallmark of sickle cell disease (SCD), with increasing recognition that a significant portion of SCD patients develop chronic pain. In the landmark PiSCES study (Smith et al), patients reported pain on 55% days, with ~30% reporting pain on >90% days. Thus, the episodic, nociceptive pain (VOE) in younger patients, evolves into a chronic pain syndrome, with neuropathic and centralized components in some adults. Kutlar et al (Blood, 2014), reported on the association of different pain related phenotypes (pain diaries, frequency of hospitalizations/ED visits, pressure pain threshold) with polymorphisms in candidate genes in 167 SCD patients, providing evidence that multiple signaling pathways and mechanisms are likely involved. In this study, 12 SCD subjects with "chronic pain", defined by reported pain >50% of days in pain diaries collected over 6 months, were enrolled (SCD-CP). 17 SCD patients who did not have chronic pain (SCD-NCP), and 9 non-SCD African-Americans (C) were enrolled as controls. Informed consent was obtained. Age, gender, Hb F levels, HU usage, and pressure pain algometer readings were recorded from SCD subjects. 8 ml of blood (EDTA) was collected from subjects at "steady state" and from normal controls. Plasma was separated and kept at -80 C until the assay. Plasma tryptase and Substance P levels were assayed by ELISA using kits from Biomatik, Inc. (catalog # EKU07922) and Enzo Life Sciences (Catalog #ADI-900-018), respectively. SCD-CP patients were significantly older than SCD-NCP: mean age 41 vs 32.2 (p=0.033). The pressure pain algometer readings did not differ significantly between SCD-CP and SCD-NCP at three sites (trapezius, ulna, masseter, p= 0.67-0.74). There were 12/17 patients on HU (70.6%) among SCD-NCP, and 6/12 (50%) among SCD-CP (p=0.435). Similarly, Hb F levels were not significantly different (14.7% in SCD-CP, vs 11.7% in SCD-NCP, p=0.446). Opioid use (average morphine equivalent as mg/day) was significantly higher in the chronic pain group (11.45 mg/day, vs 2.92 mg/day, p=0.015). Plasma tryptase and substance-P levels are shown in the table: Table 1. Tryptase (pg/ml) Substance-P (pg/ml) SCD-CP 1388.6 ±519.8 7221.1±7742.7 SCD-NCP 1023.64±221.04 5983.1±3473.0 Control 768.9±416.16 3939.7±1350.1 The difference in substance-P levels did not reach significance across groups by ANOVA (p=0.337) or in pairwise comparison between groups. However, tryptase levels were significantly different across groups by ANOVA (p=0.00615). Pairwise comparisons between two groups showed that tryptase levels were significantly different between SCD-CP and controls (p=0.0053). These results highlight characteristics of SCD patients with chronic pain: they are older, have a higher use of opioids, and have significantly higher tryptase levels. These observations support previous findings that age is a significant factor in transition to chronic pain in SCD. Higher dose of opioid use in SCD-CP could result from dose escalation to control pain; conversely, it could be argued that higher opioid use itself could be a factor in development of chronic pain through opioid-induced hyperalgesia. To our knowledge, this is the first study of plasma tryptase levels in SCD, in relation to different pain phenotypes. Tryptase is released into plasma with degranulation of mast cells and leads to inflammation, anaphylaxis, urticaria, and neuropathic pain. It binds PAR2 (protease activated receptor 2), releasing inflammatory mediators and substance P, inducing neurogenic inflammation. Elevated tryptase levels are found in systemic mastocytosis, and the newly recognized Mast Cell Activation Syndrome (MCAS). Vincent et al (Blood, 2013) showed that mast cell activation played an important role in neurogenic inflammation and chronic pain in a mouse model of SCD. They also demonstrated that inhibition of mast cell activation, via c-kit knockout or with imatinib or cromolyn sodium improved neurogenic inflammation and chronic pain. Two recent case reports (Murphy et al, Stankovic et al) document significant improvement in pain in SCD patients who developed CML, during treatment with imatinib. These observations, and the findings of our pilot study, not only suggest a novel mechanism and biomarker for chronic pain in SCD, but also a potential therapeutic target by inhibition of mast cell activation via c-kit pathway, or stabilization with cromolyn. Disclosures No relevant conflicts of interest to declare.

Mast cell–mediated inflammatory responses require the α2β1 integrin

Blood ◽  
2004 ◽  
Vol 103 (6) ◽  
pp. 2214-2220 ◽  
Author(s):  
Brian T. Edelson ◽  
Zhengzhi Li ◽  
Loretta K. Pappan ◽  
Mary M. Zutter
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Biology ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Neutrophil Migration ◽  
Mast Cell Activation ◽  
Integrin Subunit ◽  
Peritoneal Mast Cells ◽  
Α2β1 Integrin

Abstract Although the α2β1 integrin is widely expressed and has been extensively studied, it has not been previously implicated in mast cell biology. We observed that α2 integrin subunit-deficient mice exhibited markedly diminished neutrophil and interleukin-6 responses during Listeria monocytogenes– and zymosan-induced peritonitis. Since exudative neutrophils of wild-type mice expressed little α2β1 integrin, it seemed unlikely that this integrin mediated neutrophil migration directly. Here, we demonstrate constitutive α2β1 integrin expression on peritoneal mast cells. Although α2-null mice contain normal numbers of peritoneal mast cells, these α2-null cells do not support in vivo mast cell–dependent inflammatory responses. We conclude that α2β1 integrin provides a costimulatory function required for mast cell activation and cytokine production in response to infection.

scholarly journals Acupuncture Led Attenuation of Inflammatory and Nociceptive Peripheral and Central Microenvironment in Sickle Mice

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2169-2169
Author(s):  
Ying Wang ◽  
Jianxun Lei ◽  
Yann Y Lamarre ◽  
Ritu Jha ◽  
Fei Peng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mast Cell ◽  
Pain Relief ◽  
Substance P ◽  
Inflammatory Response ◽  
Cell Activation ◽  
Culture Medium ◽  
Neurogenic Inflammation ◽  
Mast Cell Activation ◽  
Skin Biopsies

Abstract Background: Inflammation, neurogenic inflammation and pain remain challenging to treat in sickle cell disease (SCD). Alternative therapies including acupuncture have been used for centuries to reduce pain and ameliorate underlying pathobiology of many disorders. We examined the mechanisms underlying acupuncture therapy in sickle mice. To prevent the influence of anesthetics and constraint on the pathobiology we developed electroacupuncture (EA) treatment for awake/conscious freely moving mice to simulate treatment conditions in patients, and then examined the peripheral and central mechanisms of neuroinflammation and nociception. Methods: HbSS-BERK sickle and HbAA-BERK control mice were treated with four EA treatments (every 3rd day, frequency: 4 or 10 Hz, pulse width: 100 microsecond, duration: 30 min) at acupoint GB30. Untreated and sham-EA treated (acupuncture without electrical stimulation) were used as controls. Hyperalgesia was evaluated daily by determining mechanical threshold, deep tissue hyperalgesia and thermal hyperalgesia using von Frey filaments, grip force, and cold plate, respectively. Blood and tissues were collected for analysis after four sessions of treatment. Skin biopsies were incubated overnight and culture medium was analyzed for mast cell activation marker tryptase, and neuromodulatory marker substance P. Results: Varied analgesic response to EA treatment was observed in sickle mice. About 86% treated mice equally showed positive (>50% pain relief) or moderate (20-30% pain relief) response and 14% were non-responsive (<20% pain relief) to EA. In positive responders, EA significantly reduced white blood cells (p<.001 Vs moderate- and non-responders), serum amyloid protein (p<.01 Vs untreated), IL-1beta (p<.05 Vs untreated, p<.01 Vs non-responders), and substance P (p<.05 Vs untreated and p<.001 Vs non-responders and p<.05 Vs moderate-responders). Concurrently, spinal cord analysis of EA treated positive-responders showed reduced substance P (p<.05 Vs untreated and non-responders), IL-1 beta (p<.01 Vs untreated), TNF alpha (p<.05 and p<.01 Vs moderate- and non-responders, respectively). Consistent with this central and peripheral anti-inflammatory response, culture medium from skin biopsies of positive responders demonstrated reduced substance P (p<.01 Vs moderate- and non-responders) and tryptase (p<.01 Vs untreated, moderate- and non-responders), and significantly less toluidine blue stained degranulating mast cells in the skin (p<.05 Vs untreated and non-responders) suggestive of attenuation of mast cell and peripheral nervous system activation. Functionally, capsaicin and substance P-induced neurogenic inflammation were significantly attenuated in positive-responders vs non-responders (p<.05) or untreated (p<.05). Peripheral and central attenuation of inflammatory and neurogenic response to EA was accompanied by inhibition of nociceptive signaling in the spinal cord. Spinal phosphorylation of p38 MAPK decreased in EA treated mice (p<.05 Vs sham-EA and untreated control; and positive-responders Vs non-responders). Conclusions: EA treatment on conscious free-moving mice simulates clinical conditions in patients and excludes the potential influence due to restraint or anesthetics. EA leads to peripheral and central neuromodulation and anti-inflammatory response by attenuating mast cell activation, substance P, and cytokine release in the periphery and by abrogating spinal nociceptive signaling of p38MAPK and inflammation. Together, these molecular and cellular effects lead to EA-induced attenuation of neurogenic inflammation and hyperalgesia in sickle mice. Importantly, these data explain the cause of variable effectiveness of EA in SCD. Disclosures No relevant conflicts of interest to declare.

Abstract 471: Systemic Chymase Inhibition Directs Atherosclerotic Plaques Towards a Stable Phenotype in ApoE Deficient Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Ilze Bot ◽  
Sandra H van Heiningen ◽  
Jurgen Fingerle ◽  
Hans Hilpert ◽  
Theo van Berkel ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Control Diet ◽  
Mast Cell Activation ◽  
Human Coronary Artery ◽  
Plaque Stability ◽  
Peritoneal Mast Cells ◽  
Chymase Inhibitor

Activated mast cells have been identified at the site of rupture in human coronary artery plaques and appear to contribute considerably to plaque progression and stability. We and others have previously demonstrated that the mast cell constituents chymase and tryptase promote apoptosis of plaque cells. In this study, we aimed to investigate whether inhibition of mast cell chymase by a specific chymase inhibitor indeed has a beneficial effect on plaque stability. Preincubation of 48/80 activated MC/9 murine mast cells or freshly isolated peritoneal mast cells with chymase inhibitor RO5010226 – 000 – 004 (RO501; 1 μM) inhibited mast cell activation, as illustrated by a decreased β-hexosaminidase activity in the releasate (−41% compared to control MC/9 cells, *P=0.04, and −80% compared to control peritoneal mast cells, *P=0.02) as well as chymase release and activity (−71% and −65%, *P=0.04, respectively). Next, we addressed whether chymase inhibition also was effective in vivo. Atherosclerotic carotid artery lesions were induced in ApoE −/− mice by perivascular collar placement; during lesion development mast cells were activated by a DNP challenge once weekly for 4 weeks. Concomitantly, a subset of mice received the chymase inhibitor (50 mg/kg/day, n=14) as diet supplement, leading to continuous serum concentrations of ~2 μM or control diet (n=12). After 6 weeks, the advanced plaques were analyzed for size and stability. While plaque size did not differ, collagen content of the lesions was 2-fold enhanced in mice treated with the chymase inhibitor compared to controls (RO501: 1.4 ± 0.5% versus controls: 0.7 ± 0.2%). This was accompanied by a significant decrease in necrotic core size of the plaques (RO501: 52 ± 3% versus controls: 41 ± 4%, *P=0.04) as well as by an increased plaque cellularity (RO501: 2.6 ± 0.1*10 3 versus controls: 2.3 ± 0.1*10 3 cells/mm 2 tissue). In agreement with these data we did observe increased peritoneal leukocyte numbers in the RO501 treated mice (RO501: 4.2 ± 1.1*10 6 cells versus 2.2 ± 0.3*10 6 cells in controls, *P=0.04). In conclusion, our data suggest that chymase inhibition indeed results in enhanced plaque stability, identifying chymase inhibition as a new therapeutic approach in the prevention of acute coronary syndromes.

Regulation of Plasma Substance P and Skin Mast Cells by Odorants

2003 ◽  
Vol 7 (4) ◽  
pp. 287-291 ◽  
Author(s):  
Junichi Hosoi ◽  
Masahiro Tanida ◽  
Toru Tsuchiya
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Substance P ◽  
Cell Activation ◽  
Immobilization Stress ◽  
Skin Diseases ◽  
Skin Inflammation ◽  
Mast Cell Activation ◽  
Itch Sensation ◽  
Methyl Benzene

Background: Mast cells stimulate inflammation and itch sensation in the skin by releasing various mediators when they are activated. Stress exacerbates some skin diseases. We have reported that inhalation of certain odorants modulates immune reactions in the skin. Objective: The possible usage of odorants in the regulation of skin inflammation and itch sensation was to be examined. Methods: Female volunteers were subjected to interview stress with or without odorant inhalation. Mice were immobilized while inhaling odorants. Toluidene blue-stained sections were analyzed for activated mast cells. Plasma substance P level was determined by enzyme-linked immunoassay. Results: Interview stress induced plasma substance P only in volunteers who did not inhale odorants containing 2% 1,3-dimethoxy-5-methyl benzene (DMMB). Immobilization stress induced mast cell activation in mice and the activation was blocked by exposure to DMMB. Conclusions: Stress causes mast cell activation via an increase in substance P. The effect of stress is suppressed by inhalation of DMMB.

scholarly journals Mast cell activation contributes to sickle cell pathobiology and pain in mice

Blood ◽  
2013 ◽  
Vol 122 (11) ◽  
pp. 1853-1862 ◽  
Author(s):  
Lucile Vincent ◽  
Derek Vang ◽  
Julia Nguyen ◽  
Mihir Gupta ◽  
Kathryn Luk ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Sickle Cell ◽  
Systemic Inflammation ◽  
Cell Activation ◽  
Neurogenic Inflammation ◽  
Mast Cell Activation ◽  
Pharmacological Inhibition ◽  
Key Points ◽  
Hypoxia Reoxygenation

Key Points Inhibition of mast cells with cromolyn or imatinib results in reduced systemic inflammation and neurogenic inflammation in sickle mice. Pharmacological inhibition or genetic depletion of mast cells in sickle mice ameliorates chronic and hypoxia/reoxygenation-induced pain.

Toll-Like Receptor 4 Knockout Attenuates Neurogenic Inflammation and Hyperalgesia In Sickle Mice

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 732-732 ◽  
Author(s):  
Derek Vang ◽  
Rocio D Saavedra Pena ◽  
Sonia A Robiner ◽  
Kalpna Gupta
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Evans Blue ◽  
Cell Activation ◽  
Neurogenic Inflammation ◽  
Vascular Dysfunction ◽  
Mast Cell Activation ◽  
Deep Tissue ◽  
Toll Like Receptor 4 ◽  
Normal Human

Abstract Pain in sickle cell anemia (SCA) is accompanied by inflammation, vascular dysfunction and ischemia/reperfusion (IR) injury. We found that activated cutaneous mast cells in HbSS-BERK sickle mice release cytokines and neuropeptides and stimulate Evans blue leakage from the vasculature resulting in neurogenic inflammation and hyperalgesia (Vincent et al., 2013, Blood). Toll-like receptor 4 (TLR4) signaling stimulates mast cell activation and plays a causative role in inflammatory and neuropathic pain. Skin mast cells and spinal cords from HbSS-BERK sickle mice showed a several-fold increase in gene expression of TLR4 transcripts as compared to control mice expressing normal human hemoglobin (p<0.001 & 0.01, respectively). We hypothesized that TLR4 mediates mast cell activation-induced neurogenic inflammation and hyperalgesia in SCA. In TLR4 knockout (KO) mice, response to lipopolysaccharide and thermal and mechanical stimuli is attenuated; and spinal glial activation and release of inflammatory cytokines are reduced with accompanying resistance to IR injury. We backcrossed HbSS-BERK mice expressing human sickle hemoglobin and HbAA-BERK control mice expressing normal human hemoglobin with TLR4-KO mice to obtain HbSS-BERK with TLR4-KO (TLR4-KO-SS), and littermate TLR4-KO, HbSS-BERK and HbAA-BERK to examine the contribution of TLR4 to chronic pain and IR-induced acute pain in SCA. Pain behaviors included grip force measurement for deep tissue pain, mechanical sensitivity to von Frey filaments for cutaneous hyperalgesia and sensitivity to heat and cold for thermal hyperalgesia, as described by us for sickle mice (Kohli et al., Blood 2010). The measure of mechanical threshold and suprathreshold to a 1.0 g von Frey fiber showed a significant reduction in mechanical sensitivity in TLR4-KO-SS as compared to HbSS-BERK (p<0.001 for both measures). Similarly, deep pain and thermal sensitivity were significantly reduced in TLR4-KO-SS as compared to HbSS-BERK (p<0.01 for each measure). All pain profiles in TLR4-KO-SS were similar to HbAA-BERK and TLR4-KO, suggestive of a contribution of TLR4 in chronic pain in sickle mice. We next examined pain evoked by hypoxia/reoxygenation (HR) simulating acute pain following vasoocclusive crisis (VOC). HR evoked a significant increase in mechanical and heat sensitivity and in deep tissue pain in HbSS-BERK mice, which was sustained for 7 days, last period of observation (p<0.05 Vs baseline at normoxia). In contrast, TLR4-KO-SS did not show a significant increase in any of the pain measures following HR, suggesting that TLR4 mediates HR-induced injury in SCA. To analyze neurogenic inflammation we quantified the leakage of Evans blue dye in response to PBS, substance P (SP) and capsaicin in the skin, 7 days after the incitement of HR. PBS-treated skin showed significantly increased leakage of Evans blue following HR in HbSS-BERK, as compared to HbSS-BERK under normoxia (p<0.01). In contrast, Evans blue leakage following HR in TLR4-KO-SS was significantly reduced as compared to HbSS-BERK under HR as well as under normoxia (p<0.01 and 0.05, respectively). In TLR4-KO-SS, SP- and capsaicin-induced Evans blue leakage was approximately 50% that of HbSS-BERK, following HR, demonstrating that TLR4 contributes to neurogenic inflammation in sickle mice. TLR4 is also expressed on endothelial cells of the vasculature, which may contribute to HR-evoked vascular dysfunction directly and also via neurogenic inflammation caused by mast cells and peripheral nerve fibers. We observed that mast cell degranulation was reduced by ∼50% in TLR4-KO-SS as compared to HbSS-BERK (p<0.001) and the number of mast cells were reduced by ∼90% in TLR4-KO-SS as compared to HbSS-BERK (p<0.001) under HR. It is likely that TLR4 also mediates the recruitment, and/or proliferation of mast cells in addition to activating the existent mast cells. Together, these data suggest that TLR4 contributes to mast cell degranulation, neurogenic inflammation and hyperalgesia in sickle mice. Therefore, targeting TLR4 with novel pharmacological antagonists/agents may reduce inflammation and pain and prevent IR injury in SCA. Disclosures: No relevant conflicts of interest to declare.

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).

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