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Biomedical subjects

L Enerbäck

Publications and source records attributed to L Enerbäck.

At least 19 recordsLinked to original sources
PubMed1992

Mast cells and eosinophils in the allergic mucosal response to allergen challenge: changes in distribution and signs of activation in relation to symptoms.

An allergen challenge was performed in 10 asymptomatic patients with strictly seasonal allergic rhinitis. For comparison; seven nonallergic subjects were challenged with allergen, and seven allergic patients were challenged with diluent. Cell samples, obtained with use of a brush technique to recover cells from within the epithelium and nasal lavage to collect cells from the epithelial surface, and symptom scores were taken before challenge and at 2-hour intervals during 12 hours. The cell suspensions were cytocentrifuged onto object slides for light microscopy. Histamine was determined in the cell pellets. In brush samples from the allergic patients challenged with allergen, eosinophils, expressed as a percentage of the total granulocytes, increased from 4.3% +/- 2.7% (mean +/- SEM) to 10.3% +/- 3.8% (p < 0.05) 4 hours after challenge. This level was maintained for up to 12 hours. A similar increase was noted in the lavage specimens 2, 6, and 8 hours after the challenge. In the brush samples the proportion of eosinophils containing two or more cytoplasmic vacuoles, taken as a sign of activation, increased from 20% to 72% (p < 0.05) 8 hours after provocation. In brush samples from the allergic patients challenged with allergen, the numbers of metachromatic cells increased to a maximum of eightfold at 10 hours. In the lavage specimens, no metachromatic cells were observed before provocation, but they progressively increased in number 2 to 12 hours after provocation. Cell pellet histamine content decreased temporarily 2 to 4 hours after challenge (p < 0.05) in brush samples from allergen-challenged allergic patients. The local metachromatic cell density before challenge, as reflected in the brush specimens, correlated with nasal congestion, sneezing, and the degree of eosinophilia.

Adult↗
PubMed1990

DNA content and nuclear size of megakaryocytes in thrombocythaemia.

Total nuclear DNA content and nuclear size of megakaryocytes were studied in biopsies of the iliac bone marrow of individuals with normal or increased platelet counts. The DNA content was determined using Feulgen cytophotometry of bone marrow smears and the nuclear area by morphometric analysis of megakaryocytes of bone marrow sections. The mean DNA content and the mean nuclear area were both significantly larger in megakaryocytes of patients with thrombocytosis as a result of myeloproliferative disease than in patients with secondary thrombocytosis as well as in two control groups of individuals with normal platelets counts, one comprising healthy volunteers, the other with various non-haematological disorders. There was a statistically significant correlation between the DNA content and nuclear area of the megakaryocytes (r = 0.92) in the entire group of bone marrows studied.

Adolescent↗
PubMed1990

Mast cells, tissue histamine and eosinophils in early- and late-phase skin reactions: effects of a single dose of prednisolone.

Skin prick tests with allergen and histamine were performed on the volar aspect of the forearms in a double-blind, cross-over study with 40 mg of prednisolone and placebo in 16 pollen-allergic subjects. Skin biopsies were taken before any treatment and 15 min (group 1; n = 8) and 6 h (group 2; n = 8) after local challenge with allergen, corresponding to the timing of an early- and late-phase reaction. The specimens were used for the histological evaluation of mast cell and eosinophil density as well as for the determination of the histamine and protein content. The size of the induced weal and flare area as well as of any late-phase reaction was determined using digitized planimetry. The single dose of prednisolone, given 2 h prior to challenge, did not affect the size of the weal and flare response. Only 4 of the individuals developed a visible late-phase response. Eosinophils were virtually absent before allergen exposure, but were already present 15 min after allergen challenge, largely associated with the blood vessels, and were numerous at 6 h. There was, however, no relationship between eosinophil density and the presence or extent of any visual late phase. The mast cells/basophils showed a tendency to increase at the 6-hour determination. The infiltration of eosinophils was blocked by the glucocorticoid. This treatment also induced a difference in the mast cell density at the 6-hour determinations, associated with a similar difference in the histamine content of the biopsy specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Nasal mast cell response to natural allergen exposure.

A redistribution of mast cells into the epithelium and towards the mucosal surface was previously observed during the allergy season in individuals allergic to birch pollen. We have therefore attempted to investigate in greater detail the role of mast cells in mucosal allergy by the study of the morphological and biochemical changes that occur in the nasal mucosa of allergic individuals during natural allergen exposure. An activation of the intraepithelial mast cells was indicated by the observation of ultrastructural signs of a secretory activity. We also found that the normal strong correlation between mast cell numbers and histamine content in the nasal mucosa was absent in specimens taken during allergen exposure, which was interpreted as a result of a release of histamine from the mast cells with the appearance of a transient, non-mast cell pool of tissue histamine. Furthermore, the histamine content of the nasal mucosa during the pollen season was strongly correlated to the severity of symptoms experienced by the patients. These observations provide additional evidence that mucosal mast cells have a pathogenetic role in continuous allergic airway disease.

Allergens↗
PubMed1989

Effect of nedocromil sodium on the compound exocytosis of mast cells.

The secretory activity of peritoneal mast cells was studied in vitro after challenge with compound 48/80 of cells obtained from normal rats and with anti-rat IgE of cells obtained from rats hyperimmunised with Nippostrongylus brasiliensis. Peritoneal mast cells were isolated from 2 groups of rats aged 2 to 3 months and 5 to 6 months. After purification, the cells were preincubated with or without nedocromil sodium for 5 minutes followed by addition of secretagogue and incubation for an additional period of 5 minutes (compound 48/80) or 15 minutes (anti-IgE). The secretory response was analysed by measurement of the release of endogenous histamine and serotonin (5-hydroxytryptamine) into the medium using high performance liquid chromatography, and by the assay of the heparin content of individual mast cells by cytofluorometry, using the fluorescent dye berberine as a quantitative marker. Concentrations of secretagogues which gave 30 to 40% amine release in controls without inhibitor were selected. In agreement with previous reports, the degree of release of histamine was slightly higher than that of serotonin, but nedocromil sodium suppressed the release of both amines in a parallel manner, without any differential effect, after stimulation with both compound 48/80 and anti-IgE. The effect of nedocromil sodium was concentration-dependent, with the lowest effective concentration in the range of 10(-8) to 10(-7) mol/L, and reduced release to about 40% of control values. Mast cells from young rats responded with a significantly higher amine release than mast cells from old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

A brush method to harvest cells from the nasal mucosa for microscopic and biochemical analysis.

A method is described for the sampling of epithelial cells and other effector cells from the human airway mucosa for structural and biochemical analysis. The cell samples are obtained from the nasal mucosa using a small nylon brush which is rotated over the epithelium and soaked and shaken in a small volume of a balanced salt solution. Morphological evaluation using light microscopy and transmission electron microscopy revealed excellently preserved cytological detail. In asymptomatic individuals the cells harvested were as follows: 45 +/- 5.9% (mean +/- SEM) epithelial cells, 38 +/- 7.1% granulocytes, 16 +/- 2.3% large mononuclear cells (monocytes), and 1.3 +/- 2.3% eosinophils. Repeated measurements in the same individual revealed a coefficient of variation of the order of 40% for the proportions of cells harvested. In comparison with nasal airway lavage, a higher proportion of epithelial cells and monocytes were obtained with the brush method. The cells harvested could also be used for biochemical analysis. The histamine content of the cell pellets was found to be strongly correlated with the mast cell count (r = 0.93) and was estimated to about 10 pg/cell, which is higher than previously reported for mast cells obtained from human lung tissue dispersed by an enzymatic method. The present method appears to be appropriate for the study of cellular events in the nasal mucosal epithelium.

Adult↗
PubMed1988

Phenotypic expression of proteoglycan in mast cells of the human nasal mucosa.

The phenotypic expression of the proteoglycan of human mast cells in the nasal mucosa and normal skin was analysed using histochemical techniques. Nasal mucosa was obtained from normal subjects, from patients with seasonal allergic rhinitis before and during the pollen season and from patients with nasal polyps. In the latter groups, specimens were taken from both polyp tissue and adjacent nasal mucosa. Formaldehyde treatment blocked the cationic dye binding in 75-84% of the mast cells located in the nasal mucosa, as compared to the optimum fixation with IFAA (iso-osmotic formaldehyde-acetic acid). A significantly lower degree of blocking of dye binding was obtained in the human skin where 45% of the mast cells were susceptible to formaldehyde treatment (P less than 0.01). The mast cells of the polyp tissue also showed a relatively low degree of blocking (54%), which was significantly lower than the blocking of mast cells of the nasal mucosa taken from the same individuals (P less than 0.05). Staining of serial tissue sections in Alcian Blue containing graded concentrations of MgCl2 was used to determine the critical electrolyte concentration (CEC) of the dye binding, defined as the salt concentration at which the staining of 50% of the mast cells is extinguished. The CEC of the skin mast cells was 0.64M MgCl2 which is significantly higher than that of the mast cells of the nasal mucosa of normal subjects [0.49M (P less than 0.05)], allergic subjects [0.52M (P less than 0.01)], patients with polyp disease [0.52M (P less than 0.01)] and the polyp tissue proper [0.57M (P less than 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Secretory activity of nasal mucosal mast cells and histamine release in hay fever.

Although theoretical considerations and experimental evidence implicate the mast cells in the pathophysiology of the immediate type hypersensitivity reaction, the evidence of their active participation in human allergic disease is still fragmentary. We have therefore sought evidence of mast cell activation in allergic mucosal disease using strictly seasonal allergic rhinitis as a model. Twelve patients with birch pollen-induced hay fever were examined before and well into the birch pollen season. Allergen exposure was monitored by pollen counts and the degree of symptoms registered daily. Small surgical biopsies and mucosal imprints were obtained from each patient before and during the season. Mast cells were analysed by light and electron microscopy and mucosal histamine was measured using a sensitive HPLC assay. We found a reduction in the number of mast cells in the nasal mucosa during pollen exposure (p less than 0.05) but no significant reduction of the histamine content. There was a correlation between the nasal mucosal mast cell density and histamine content before the pollen season (r = 0.76; p less than 0.01), but no such correlation was found during the period of pollen exposure (r = 0.19; n.s.). This finding points to secretory activity by the mast cells during the pollen season and to the appearance of a non-mast cell pool of tissue histamine. Evidence for a secretory activity of the mast cells during the pollen season was also confirmed by electron microscopy. In addition, we found a strong correlation (r = 0.77; p less than 0.01) between the histamine content of the nasal mucosa during the pollen season and the degree of nasal symptoms. The number of epithelium-associated mast cells found on mucosal imprints prior to the pollen season showed a strong correlation with the symptoms experienced later during the period of pollen exposure (r = 0.83; p less than 0.01). Taken together these observations indicate that the mast cell has a pathogenetic role in continuous allergic airway disease and re-emphasizes the role of histamine in the induction of the symptoms of allergic rhinitis.

Adult↗
PubMed1987

Mucosal mast cells in the rat and in man.

The proteoglycan structure of mucosal mast cells (MMC) of the two species has been analyzed with histochemical in situ techniques. The findings indicate that human MMC, like human mast cells of several other sites, contain a heparin proteoglycan, unlike rat MMC which lack heparin but contain an oversulphated chondroitin sulphate. However, the dye-binding of the human MMC proteoglycan, like that of the rat, is highly susceptible to blocking by formaldehyde. Human MMC also exhibit a lower critical electrolyte concentration (CEC) of dye-binding than mast cells of other connective tissue sites, suggesting a relatively lower charge density and/or molecular weight of the glycosaminoglycan of the MMC. These findings thus suggest that the human MMC like those of the rat have a distinctive proteoglycan structure. Recent findings of another group indicate that the human MMC like those of the rat have also a distinctive proteinase composition. Finally, the mast cell response of the nasal mucosa during birch pollen allergy shows fundamental similarities to the nematode response of the rat intestinal mucosa. During both conditions mast cells are redistributed from the lamina propria into the epithelium, probably as a result of migration of mast cells or mast cell precursors. Taken together, these findings suggest the existence of a distinctive MMC phenotype also in man.

Animals↗
PubMed1986

Non-differential inhibition of histamine and serotonin release from mast cells by amitriptyline.

A differential amine release from mast cells induced by an inhibitory effect of the antidepressant drug amitriptyline on the release of histamine but not on that of serotonin has recently been reported. In view of the potential biological importance of a differential release of mast cell amines we have studied the effect of amitriptyline on the dynamics of the secretory process using a combination of vital berberine staining (demonstrating intracellular granules that have released amines) and measurement of histamine, serotonin (5-HT), and heparin release. The results show a non-differential inhibition of the release of histamine and 5-HT by amitriptyline. The basic pattern of the secretory process, studied in terms of granule extrusion and amine release from intracellular granules, was unaffected by the drug.

Amitriptyline↗
PubMed1986

Dermal mast cells in mastocytosis: fixation, distribution and quantitation.

The mast cell distribution and number were studied in skin biopsies of 18 mastocytosis patients and 10 controls. The biopsies were stained for mast cells with toluidine blue at pH 0.5. The number in the upper dermis of lesional abdominal skin was at least twice as high as that of normal adjacent skin. Fixation in iso-osmotic 0.6% formaldehyde and 0.5% acetic acid, revealed more mast cells than conventional 4% formaldehyde fixation. Staining for 5 days, when compared to the normal for 30 min, increased the number of demonstrable mast cells just as did the change in fixation. Conventional formaldehyde fixation thus partially blocks the dye-binding of cutaneous mast cells, about 20% of the cells escaping detection. The degree of aldehyde blocking was similar in lesional and normal skin. A more pronounced blocking of dye-binding has been demonstrated previously in gut mucosal mast cells. Whether the blocking of dye-binding is an expression of heterogeneity in dermal mast cells remains to be determined.

Adolescent↗
PubMed1979

Long term increase of mucosal mast cells in the rat induced by administration of compound 48/80.

Administration of Compound 48/80 to rats for 5 days resulted in an increase of the specific type of mucosal mast cell, while connective tissue mast cells elsewhere were almost completely degranulated. The number of mucosal mast cells increased slowly for another 5 days and then returned to the control level, in an exponential manner. The half life of the newly formed mast cells was calculated to be about 40 days. This value may be taken as an estimate of the half life of mucosal mast cells. These cells, therefore, constitute a fraction of mast cells with rapid turnover. Available evidence indicates that the classical connective tissue mast cell has a very long life span, without significant turnover in terms of cell death and cell renewal. We suggest that the increase of mucosal mast cells is an indirect effect of Compound 48/80, related to its effect on other mast cells and mediated by material(s) released from these cells during the secretory process.

Animals↗
PubMed1979

Protein content, dry mass and chemical composition of individual mast cells related to body growth.

Recently developed quantitative microscopical techniques were used to study relations between body growth and protein content as well as dry mass of individual mast cells. Since previous studies had shown an age-related increase of mast cell content of 5-hydroxytryptamine (5-HT) and heparin, these mast cell components were also included in the present study. The cells were obtained from the peritoneal cavity of rats aged 44--269 days (body weights 189--610 g). All studied mast cell parameters showed an increase that was related to the growth of the animals. The dry mass increased 60%, protein 50%, heparin 50% but 5-HT increased as much as 260% during the studied growth period. There was a mutual and linear correlation between all studied mast cell parameters. Population studies, based on large scale measurements of individual mast cells from young and adult rats, were made. These studies showed that histograms of 5-HT content, protein content and dry mass of individual mast cells were skewed with a tail towards higher values and approximately lognormal. On the other hand, the frequency distribution of heparin content of individual mast cells was approximately normal.

Animals↗
PubMed1978

Growth related changes in the content of heparin and 5-hydroxytryptamine of mast cells.

Heparin and 5-hydroxytryptamine (5-HT) were quantitated cytofluorometrically in individual mast cells from rats of various ages and body weights. Mast cells were studied in animals 35-200 days of age (150-575 g) representing a period of major body growth and about a quarter of the life span of the rat. Mast cell numbers as well as the content of both heparin and 5-HT in the mast cells was found to be strongly related to body weight and age of the animals. The number of mast cells increased about 3.5 times, the content of heparin in mast cells was doubled and the content of 5-HT increased at least three times during the growth period studied. There were great variations in the content of heparin and 5-HT within the cell populations of both young and old animals. The heparin content in the mast cell populations appeared to be either approximately normally distributed or slightly positively skewed. The skewness was not as marked as in a log-normal distribution. The 5-HT distribution profiles, on the other hand, were more strongly positively skewed. Except in the youngest age group, the 5-HT content appeared to be log-normally distributed within the mast cell population. A strong positive correlation was found between the median values of 5-HT and heparin content in the mast cell populations of growing rats.

Aging↗