Increased Numbers Of Mast Cells Research Articles

Mast cell numbers in the mucosa of the inferior turbinate in patients with perennial allergic rhinitis: a light microscopic study

The number of mast cells in the inferior turbinate from patients with perennial allergy due to house dust mite were compared with ten normal controls. Ten random high powered fields were counted in the epithelium and the submucosa in samples which had been divided into two and fixed either in aqueous formalin or Carnoy's fixative. The sections from each block were stained with either Azure A or Chloroacetate esterase technique. No statistical differences were found. The lack of increase in mast cell numbers was attributed to degranulation since numbers have been shown to be increased in perennial allergy when sections are examined ultrastructurally.

Calcitonin Gene‐Related Peptide in the Developing and Aging Thymus

Calcitonin gene-related peptide (CGRP) is known to block Con A and PHA induced T cell proliferation. As a first step in determining the role of this peptide in T cell education and function we have studied the distribution of CGRP within the developing mouse thymus using immunocytochemistry. CGRP-like immunoreactivity (CGRP-IR) was found in the thymic nerves in close proximity to blood vessels in the 17-day-old embryonic mouse thymus. A discrete population of small cells at the cortico-medullary junction also stained intensely for CGRP. As the mouse thymus reached maturity (three to eight weeks) CGRP innervation became more dense, with fibers running along the vasculature at the cortico-medullary boundary, then branching into the cortical and medullary regions. Some fibers were invested in the blood vessels while a large portion formed varicosities among the cells of the thymus. In the mature thymus, the small CGRP-IR cortico-medullary cells were more numerous, and CGRP-IR was also found in subcapsular and trabecular mast cells. The pattern of innervation remained the same in the aging mouse thymus (six months), but there appeared to be somewhat fewer cortico-medullary cells and an increase in mast cell number. In the aged (eighteen months) thymus, the small CGRP-IR cortico-medullary cells were rarely seen, but mast cells were more numerous, most of which stained positively for CGRP, in the connective tissue. Nerves containing CGRP-IR generally had the same distribution as in the younger mice but appeared somewhat truncated. The distribution of CGRP-IR nerves in the mouse thymus at different stages of development was similar to that reported for cholinergic (AChE-positive) nerves. Since the brain-stem vagal nuclei have been shown by retrograde transport studies to project to the thymus as well as to contain CGRP-IR neurons, our findings suggest that CGRP-IR thymic nerves may be derived from the vagus complex.

Effect of long-term infusion of platelet-activating factor on pulmonary responsiveness and morphology in the guinea-pig

The effect of chronic administration of platelet-activating factor (PAF) on airway reactivity, cell recruitment and lung morphology in the guinea-pig has been investigated. Alzet osmotic minipumps delivering either PAF (7.2 mg/kg/14 days) in 0.25% (w/v) bovine serum albumin in saline (saline-BSA), acetylcholine or saline-BSA alone were implanted s.c. in the neck region of guinea-pigs and connected to the jugular vein. In some experiments, implanted and non-implanted animals were treated daily with the PAF antagonist, BN 52021 (15 mg/kg, twice a day, p.o.). On day 15 after minipump implantation, the animals were anesthetized with urethane (1.2 g/kg, i.p.) and tracheal cannula was inserted for mechanical ventilation. Pulmonary inflation pressure (PIP) was monitored and airway responsiveness was assessed by administration of increasing doses of histamine (0.2–100 μg/kg, i.v.). As compared to saline-BSA-treated or non-implanted guinea-pigs, chronic treatment of the animals with PAF induced a significant (p<0.01) increase in airway response. No significant change in airway responsiveness was observed following chronic acetylcholine administration. In contrast, regardless of the treatment of the animals, no change in the threshold dose of histamine inducing alteration in PIP was noted, suggesting that PAF induces bronchopulmonary hyperreactivity rather than hyperresponsiveness. In addition, no significant difference was observed in the in vitro responsiveness to histamine of lung parenchymal strips from animals having received PAF or saline-BSA. Histological evaluation of the lung from guinea-pigs receiving PAF exhibited moderate hyperplasia of airway smooth muscle cells, marked eosinophil infiltration and increase in mast cell number in the peribronchial zone as compared to those from control, acetylcholine- or solvent-treated animals. These alterations were markedly reduced or absent in guinea-pigs implanted with PAF-containing minipumps and concomitantly treated with BN 52021. In conclusion, chronic administration of PAF to guinea-pigs results in airway hyperreactivity to histamine in vivo, associated with structural changes in airway smooth muscle cell mass, but which is unlikely to be secondary to protracted bronchoconstriction.

Mast Cells and Scleroderma-Reply

In Reply.— Chanez and colleagues studied the lungs of patients with scleroderma. They found increased mast cell numbers in bronchoalveolar lavage fluid, but this finding did not correlate with the presence or absence of interstitial lung disease. Bronchoalveolar lavage histamine levels and mast cell numbers in bronchial biopsy specimens were not elevated in patients with scleroderma. Taken together, these results do not seem to support the hypothesis that mast cell activity is important in the fibrosis of scleroderma and other fibrotic processes. There are some points that need to be considered, and these concern the activity of the disease process. The patients of Chanez et al had been sick for 15 to 29 years, and one cannot tell if they are in the active, the quiescent, or the resolving stage of the disease. If their disease is quiescent, the hypothesis would not predict any increase in mast cell numbers

Mast Cells in Normal and Pathological Specimens of the Equine Lung

In lungs from 22 horses, the number and type of mast cells in histologically normal specimens were compared with those in specimens with various histological lesions. Tissues fixed in Carnoy's solution were superior to those fixed in formalin for the identification of mast cells. Fixation of lung specimens from eight horses in Carnoy's solution and formalin allowed the identification of two subpopulations of mast cells: formalin-sensitive, which predominated and formalin-resistant. Specimens with mild chronic tracheitis and mild and moderate chronic bronchitis generally had slight increases in mast cell numbers in comparison to histologically normal specimens. An increase in mast cell numbers was also observed around small and large bronchioles with mild, moderate and severe bronchiolitis and in fibrosed pulmonary pleurae in comparison to specimens with no histological lesions. The most striking increase in mast cell numbers was seen in fibrosed alveolar septa; there were approximately four times as many mast cells in these specimens as in specimens with normal histology.

Mast Cells and Fibrosis: The Relevance to Scleroderma

Mast cells are being recognized as important constituents in fibrotic processes. This article reviews the evidence for increased mast cell numbers and/or function in a variety of fibrotic conditions. Increased mast cell numbers and activity are seen in chronic murine graft-versus-host disease (a model for scleroderma) and in active scleroderma itself. An integrated schema for scleroderma is presented, emphasizing the interactions among mast cells, endothelial cells, and fibroblasts mediated by heparin and heparin-binding growth factors.

Mast cells in the testis, epididymis and accessory glands of the rat: effects of neonatal steroid treatment.

Mast cells in the testis of control adult rats were found almost exclusively around subcapsular blood vessels. Discrete mast cells were distributed throughout the stroma of the epididymis and sex accessory glands. In neonatally estrogen-treated rats, a greater number of mast cells was present in the testicular interstitium, whereas no significant increase in the number of mast cells per square millimeter of stroma was found for the epididymis and sex accessory glands, despite stromal proliferation. On the other hand, androgen-treated rats did not have increased mast cell numbers in any organ. These results indicate that the increase in mast cell numbers was estrogen-dependent, specifically related to the testis and did not seem to be a consequence of the increase in the connective interstitial tissue.

Hematopathology of the Bone Marrow in Pediatric Cutaneous Mastocytosis: A Study of 17 Patients

Sixteen bone marrow aspirates and 15 trephine core biopsies from 17 children with cutaneous mastocytosis, of which 15 exhibited urticaria pigmentosa and 2 exhibited diffuse cutaneous mastocytosis, were evaluated for the presence of bone marrow-associated pathologic conditions. Eight bone marrow aspirates from 8 children and 23 trephine core bone marrow biopsies from 16 children who had had evaluation for hematologic abnormalities not associated with cutaneous mastocytosis served as a control population. Eosinophilia was a prominent finding in bone marrows of 9 of 17 patients who had cutaneous mastocytosis. Increased mast cell numbers in bone marrow aspirates were observed in 5 children with cutaneous mastocytosis (5 of 16) and in 2 of the control children (2 of 8). Examination of the trephine core bone marrow biopsies obtained from patients with cutaneous mastocytosis demonstrated focal perivascular and paratrabecular aggregates consisting of mast cells, eosinophils, and early myeloid cells in 10 of 15 individuals. Similar lesions were observed in trephine core bone marrow biopsies of 3 of 16 control patients. The focal mast cell lesions characteristic of adult systemic mastocytosis were not observed. The authors conclude that cutaneous mastocytosis in the pediatric age group is rarely associated with definitive bone marrow findings suggestive of systemic mast cell disease and that this observation is consistent with previous reports that cutaneous mastocytosis in the majority of pediatric cases resolves by adulthood.

Increased mast cell numbers in the sclerotic skin of porphyria cutanea tarda.

We quantitated numbers of mast cells in the sclerotic skin noted on the dorsa of the hands of 10 patients with porphyria cutanea tarda (PCT), and compared them with those of diffuse scleroderma and healthy controls. Mast cell counts in sclerodermoid skin of PCT patients were significantly greater than those in involved skin of 9 patients with diffuse scleroderma in its late stage and also greater than those in normal skin of 8 controls. When mast cell density was analyzed according to the depth of the dermis, an 84% increase was noted in the uppermost layer (0-0.2 mm in depth) and a 150% increase in the second uppermost layer (0.2-0.4 mm in depth) in the patients with PCT when compared with those in the corresponding sites of the controls. These results suggest a possible role of mast cells in the pathogenesis of sclerodermoid skin of PCT.

Antigen-induced contraction of jejunal smooth muscle in the sensitized rat.

We examined contractility of longitudinal muscle strips of jejunum from control rats and rats infected 34-85 days previously with Trichinella spiralis. Antigen prepared from T. spiralis larvae contracted muscle from previously infected but not control rats. Contraction was specific for the sensitizing agent because antigen from Nippostrongylus brasiliensis did not induce contraction. Contraction was resistant to atropine or tetrodotoxin but was inhibited by the 5-hydroxytryptamine (5-HT) antagonist cyproheptadine and by 5-HT desensitization. Neither histamine antagonists, diphenhydramine (H1-receptor antagonist) or ranitidine (H2-receptor antagonist), nor indomethacin, a prostaglandin synthase inhibitor, influenced the antigen response. In Trichinella-infected rats there was a significant increase in mast cell number in the muscle layers, and the contraction induced by T. spiralis antigen was inhibited by the mast cell stabilizer doxantrazole. In addition, anti-rat immunoglobulin E serum, compound 48/80, and concanavalin A each contracted muscles from rats previously infected with T. spiralis. These results are consistent with the hypothesis that T. spiralis infection leads to mast cell proliferation in the muscle layers and that subsequent exposure to antigen results in mast cell degranulation, 5-HT release, and contraction of smooth muscle.

A survey of the number and distribution of mast cells in the skin of patients with mast cell disorders

It has been suggested that patients who present with episodes of unexplained anaphytaxis (UEA) or unexplained flushing (UEF) have systemic mastocytosis (SM), a proposal believed to be supported by the presence of excess mast cell (MC) numbers in the skin of these individuals. To examine this hypothesis, we determined the number and distribution of MCs in the skin of nine normal subjects, nine patients with UEA/UEF, six patients with urticaria pigmentosa (UP), and 14 patients with SM. Skin biopsy specimens of normal subjects contained 38.4 ± 4 ( x ± SEM) MCs per square millimeter. Biopsy specimens of patients with UEA/UEF contained 71.8 ± 13 MCs per square millimeter. Although the numbers were significantly different from numbers in skin of normal subjects ( p < 0.05), similar modest increases in MC numbers are observed in a number of skin conditions. In marked contrast, lesional biopsy specimens of patients with UP contained 596.5 ± 278 MCs per square millimeter ( p < 0.05, n = 6, compared to MC numbers in the skin of normal subjects), and patients with SM had 720.6 ± 176 MCs per square millimeter in lesional skin ( p < 0.01, n = 12, compared to normal skin). Patients with UP or SM also had increased MC numbers in nonlesional skin compared to normal skin (168.0 MCs per square millimeter, p < 0.05, n = 5, and 184.4 MCs per square millimeter, p < 0.01, n = 10, respectively). Analysis of the relationship between MCs and blood vessels (BV) suggested that MCs in patients with mastocytosis first increase around BVs and later appear in tissues distant from BVs. Patients with UEA/UEF had an average plasma histamine level of 246.3 ± 51 pg/ml, not significantly different from the average plasma histamine level in normal subjects (262.0 ± 19, n = 76). Patients with UP and SM had plasma histamine levels of 402.5 ± 176 pg/ml and 2032.9 ± 491 pg/ml, respectively, both significantly different ( p < 0.01) from normal subjects. In conclusion, although modest increases (twofold to threefold) in MC numbers are observed in the skin of some patients with UEA and UEF, patients with SM have, on average, a 15-fold to twentyfold increase in MC numbers. Rare exceptions to this observation suggest a need to correlate the gross skin examination with skin MC numbers and to diagnose SM by appropriate criteria.

Rapid increase in mast cell numbers in canine central and peripheral airways.

In preliminary studies of antigen-induced airway inflammation, we noted an apparent increase in peribronchiolar mast cell number. Experiments were thus undertaken to investigate the nature of this migration of mast cells into the central and peripheral airway epithelium and to determine its time course. The tracheae and small airways of 10 anesthetized mongrel dogs were exposed via a bronchoscope to Ascaris suum antigen (Ag), fMet-Leu-Phe (fMLP), ovalbumin (OVA), and isotonic saline (SAL). In the central airways, all stimuli provoked a significant increase (P less than 0.05) in mast cell numbers at the base of the airway epithelium within 3 h. In the peripheral airways, only Ag aerosol stimulated a significant mast cell increase compared with unexposed tissue. In a second series of experiments, the trachea of seven dogs were exposed to 0.026, 0.26, and 2.6 micrograms of Ag. The tissue was collected at 1, 3, 6, and 10 h after exposure. In these experiments, there was a significant mast cell increase seen within 1 h but it was not dose dependent. By 6-10 h after exposure, mast cell counts were not significantly different from the unexposed condition, which is consistent with the idea that some of the cells either degranulated or migrated into the airway lumen. We conclude that mast cell migration is an acute response that can be demonstrated within 1 h of stimulation with Ag. The observation that nonimmunological stimuli may, in some cases, also stimulate mast cell movement affords the possibility that this process represents a generalized response to airway irritation.

Effect of histamine on proliferation of normal human adult lung fibroblasts.

Fibrotic lung tissue shows increased connective tissue deposition and fibroblast proliferation and in addition a substantial increase in mast cell numbers in and around the fibrotic area. To elucidate the question of whether products of mast cells affect the proliferative behaviour of structural cells in the lung and thereby contribute to fibrogenesis, the effect of histamine, a prominent mast cell derived mediator, on the in vitro proliferation of primary cultures of normal adult human lung fibroblasts was studied. Histamine enhanced fibroblast proliferation in a dose dependent manner, with an optimum effect at a physiological concentration of 10(-7) mol/l. This effect occurred when cells were exposed to histamine at restricted times during cell growth and was shown to depend in part on the stage of the cell cycle reached by the fibroblasts. The histamine induced proliferation was mediated through an H2 histamine receptor on the fibroblast, being inhibited by cimetidine, an H2 antagonist, and not by pyrilamine maleate, an antagonist of the H1 receptor. Mast cell products such as histamine may interact with and promote the increased fibroblast proliferation found in pulmonary fibrosis.

Bronchoalveolar Mastocytosis in Farmer's Lung Is Related to the Disease Activity

Patients (n = 10) at the acute phase of farmer's lung were investigated with chest roentgenography, lung function tests, and bronchoalveolar lavage (BAL) fluid analysis (n = 9). They had diffuse interstitial lung infiltrates and a reduction of the diffusion capacity. The dominating recovered cell types during BAL were lymphocytes; and in two patients, granulocytes. A prominent increase in mast cell numbers was seen in all patients. After avoidance of contact with moldy plant material for four to ten weeks (n = 7), lung function started to improve; and the BAL cell counts, to decrease. At clinical remission six to 14 months later (n = 7), the chest roentgenogram was normal and the diffusion capacity was slightly subnormal. The BAL numbers of mast cells and lymphocytes had further decreased but still remained increased compared with those in the healthy controls. Parallel to the normalization of the lung function and the recovery of BAL fluid cells, the increased BAL fluid concentrations of hyaluronic acid and procollagen III peptide started to decrease. These potential markers of fibroblast activation were significantly related to the mast cell number, but not to the lymphocyte number. The study has demonstrated that pulmonary mastocytosis is a prominent finding in farmer's lung and is related to the disease activity. The observed relationship between pulmonary mastocytosis and biochemical signs of lung fibroblast activation is further evidence to support the hypothesis of a mast cell interaction with lung connective tissue.

Bronchoalveolar mastocytosis in farmer's lung is related to the disease activity

Patients (n = 10) at the acute phase of farmer's lung were investigated with chest roentgenography, lung function tests, and bronchoalveolar lavage (BAL) fluid analysis (n = 9). They had diffuse interstitial lung infiltrates and a reduction of the diffusion capacity. The dominating recovered cell types during BAL were lymphocytes; and in two patients, granulocytes. A prominent increase in mast cell numbers was seen in all patients. After avoidance of contact with moldy plant material for four to ten weeks (n = 7), lung function started to improve; and the BAL cell counts, to decrease. At clinical remission six to 14 months later (n = 7), the chest roentgenogram was normal and the diffusion capacity was slightly subnormal. The BAL numbers of mast cells and lymphocytes had further decreased but still remained increased compared with those in the healthy controls. Parallel to the normalization of the lung function and the recovery of BAL fluid cells, the increased BAL fluid concentrations of hyaluronic acid and procollagen III peptide started to decrease. These potential markers of fibroblast activation were significantly related to the mast cell number, but not to the lymphocyte number. The study has demonstrated that pulmonary mastocytosis is a prominent finding in farmer's lung and is related to the disease activity. The observed relationship between pulmonary mastocytosis and biochemical signs of lung fibroblast activation is further evidence to support the hypothesis of a mast cell interaction with lung connective tissue.

Age-dependent bone marrow mast cell maturation in specific pathogen-free rats.

In the present study we have investigated an age-dependent mast cell increase. The mast cell numbers in bone marrow from (BN x Wi/Fu)F1 rats were determined using Alcian blue staining of cells in solution. From the 6th to the 19th week of age the number of mast cells in the bone marrow increased 6-fold with a marked peak around the 12th week of age. This increase in mast cell numbers was accompanied with increased histamine levels. Immunization increased the numbers further, also when the age-dependent mast cell increase was corrected for. The results should be considered in relation to previous studies revealing increased mast cell numbers in the bone marrow after immunization and also increasing numbers in the lungs of rats immunized with protein antigens or exposed to environmental antigens.

Suppressive effect of tritoqualine (TRQ) on the acceleration of fibrosis in the liver

Liver cirrhosis was induced by consecutive CCl4-treatment of rats (0.5 ml/kg, s.c., 2 times/week) to investigate the effect of TRQ on the acceleration of fibrosis in the liver. An increase of hydroxyproline content in the liver of rats began 12 weeks after the CCl4 treatment and a 1.9-fold increase was observed at week 14 compared with non-CCl4 treated rats. Histamine in the liver increased about 2 times at week 14. Increased numbers of mast cells were seen in the area of proliferated collagen fiber in the liver under microscopic observation, and also a good correlation was recognized between the number of mast cells and the progression of fibrosis. An administration of TRQ to the rats for 2 weeks from week 13 resulted in significant suppression of both the increase in hydroxyproline and histamine in the liver dose-dependently compared with the CCl4 control group. Both progression of collagen and increase in mast cell numbers were also suppressed by TRQ dose-dependently under histopathological observation; at the same time the decrease in mast cells was recognized to correspond to the decrease in hydroxyproline and histamine in the liver. Thus, it was suggested that increased mast cells participated in the biosynthesis of collagen. Though the elevated serum transaminases, alkaline phosphatase and leucine amino peptidase were also suppressed by TRQ administration, the protein biosynthesis activity of the liver and lowered serum total cholesterol were not improved as much as the other parameters. From these results, it was shown that TRQ was especially and remarkably effective in suppressing the acceleration of fibrosis, and one of the pharmacological mechanisms of this action may be ascribed to the inhibitory effect of TRQ on the activation of mast cells by some stimulants.

An assessment of mast-cell deficient mice (W/Wv) as a model system to study the role of histamine in implantation and deciduoma formation

The ovaries from mast cell-normal (+/+) and mast cell-deficient (W/Wv) mice were examined with light and electron microscopy. In addition the effect of ovariectomy and subsequent steroid treatment on total uterine histamine content, total mast cell numbers and surface and glandular epithelial cell heights was measured. The ovaries of +/+ mice were normal, displaying various stages of follicular growth and atresia and numerous corpora lutea; the ovaries of W/Wv mice lacked follicles and corpora lutea but contained numerous hyperplastic interstitial cells which contained numerous lipid droplets, vesiculated mitochondria and abundant endoplasmic reticulum suggestive of steroid synthesis. Steroid treatment of ovariectomized +/+ and W/Wv mice caused a significant increase in uterine wet weight and endometrial surface and glandular epithelial cell heights. In +/+ mice, steroid treatment caused a concomitant increase in total mast cells per uterine horn while mast cells were totally absent in W/Wv mice. The increase in uterine histamine in +/+ mice is consistent with the increase in mast cell numbers. Measurable amounts of uterine histamine, which increases slightly after steroid treatment, were demonstrated in W/Wv mice. Since the uteri of +/+ and W/Wv mice respond to steroids in a similar manner with the sole exception being histamine content and mast cell numbers, our results demonstrate the potential of using these animals to investigate the role(s) of uterine mast cells and non-mast cell uterine histamine in the process of implantation and the formation of a decidual cell response.

Mast cells and inhalation of asbestos in rats.

Mast cell counts were performed on sections taken from the lungs of rats exposed by inhalation to different UICC samples of asbestos fibres for periods ranging from a few days to two years. A comparison of mast cell counts with grades of fibrosis showed that there is a sevenfold increase when there is interlobular linking of the fibrotic lesions (grade 5). Submesothelial mast cells showed a trend of increasing numbers with increasing exposure and with increasing subpleural thickening. Each type of asbestos produced a steady increase in mast cell numbers with increasing exposure. Two samples from animals exposed to chrysotile and two from animals exposed to amphiboles (crocidolite and amosite respectively) had 10 times as many cells as the control group after six and 24 months' exposure. Another amphibole, anthophyllite, produced 50 times more cells than were present in the control specimen appropriate for the heaviest exposure. These results are briefly discussed in relation to further exposure, smoking, and characteristics of the dusts.

Tissue histamine levels and mast cell numbers in tumour-bearing mice.

In C57BL/6 mice bearing the 3LL carcinoma and in C3H mice bearing the McC3 -1 fibrosarcoma (18th passage), the increase in skin histamine levels was correlated with the increase in mast cell number. The number of cells able to incorporate tritiated thymidine was proportional to the mast cell number. These results strengthen the notion that, in tumour-bearing rodents, the increase in tissue histamine is an active phenomenon.