Biomedical subjects

D D Metcalfe

Publications and source records attributed to D D Metcalfe.

At least 127 records · Page 7Linked to original sources

PubMed1993

Immortalization of mouse bone marrow-derived mast cells with Ad12-SV40 virus.

Mast cells arise in cultures of murine bone marrow in medium supplemented with interleukin-3 (IL-3). In the present study, we report the development of long-term mast cell lines from murine bone-marrow-derived cultured mast cells (BMCMC) following inoculation with adenovirus 12-simian virus 40 (Ad12-SV40) hybrid virus. One culture of Ad12-SV40 immortalized BMCMC (designated as MCP-5) was selected for further analysis. These transformed cells appear similar in morphology and histochemistry to the primary BMCMC from which they are derived and did not shed infectious virus into the culture supernatants. In addition, these cells synthesize predominantly chondroitin sulfate proteoglycans and contain histamine which is released following a physiologic stimulus. Limiting-dilution single-cell cloning produced five independent mast cell lines (MCP-5.1 to MCP-5.5). Southern blot analysis of genomic DNA isolated from these single-cell clones demonstrates different patterns of viral integration in all the five clones. All clones retain responsiveness to an exogenous source of IL-3 for growth and proliferation. Each single-cell clone also demonstrates a unique pattern of cytokine gene expression in response to calcium ionophore A23187 and phorbol-12-myristate-13-acetate. This suggests that within a culture of BMCMC there are differences in cytokine gene expression that vary from one cell to another. The availability of immortalized mast cell lines derived from murine bone marrow which retain their growth factor responsiveness and the ability to respond to degranulating stimuli should facilitate future studies of mast cell biology.

Adenoviruses, Human↗

PubMed1993

Cytokines and their role in the pathogenesis of severe food hypersensitivity reactions.

Cytokines are proteins produced by one cell that are capable of altering the behavior of another cell. Their biologic effects are both pleomorphic and redundant. A number of cytokines have been implicated in the genesis of allergic reactions, including IL-4, IL-5, IL-6, and tumor necrosis factor (TNF). In contrast, other cytokines such as gamma interferon (gamma-IFN) may have biologic actions that act to limit allergic responses. In studies on patients with severe food allergy, we have found cytokine production from peripheral T cells to be abnormal following mitogenic stimulation. These lymphokine abnormalities may contribute to the elevation in IgE and the eosinophilia seen in severe food allergy.

Cytokines↗

PubMed1993

Ultrastructural localization of heparin to human mast cells of the MCTC and MCT types by labeling with antithrombin III-gold.

BACKGROUND: Mast cells derived from human skin and lung have been reported to produce heparin and chondroitin sulfate E proteoglycans. However, no information about the proteoglycans distribution among the different human mast cell types (MCTC and MCT) is available. Conjugates of antithrombin III-gold were used to assess the presence of heparin in both human mast cell subsets. EXPERIMENTAL DESIGN: Thin sections of human and rodent tissues and dispersed cell preparations were labeled with the conjugate in the presence of saline, heparin, and chondroitin sulfates A and E and particle densities were measured over granules, perigranular regions, and extracellular space. Control sections were preincubated with heparinase, chondroitinase ABC, or buffer. RESULTS: Labeling with antithrombin III-gold particles was detected in essentially all granules of human mast cells in skin (predominantly MCTC type), lung alveolar wall, and bowel mucosa (predominantly MCT type), but was negligible over human eosinophils. Consistent with the known distribution of heparin in rodent mast cells, strong labeling was observed over rat peritoneal connective tissue type mast cells, but not over mucosal mast cells in bowel mucosa of Nippostrongylus brasiliensis-infected rats (which contain chondroitin sulfate di-B) nor over mouse PT-18 mast cells (which contain chondroitin sulfate E). Mast cell labeling was preferentially blocked by exogenous heparin, and virtually abolished by heparinase but not chondroitinase ABC preincubation. CONCLUSIONS: The data with rodent mast cells indicate that antithrombin III-gold labels cells that contain heparin, but not those that contain only over-sulfated chondroitin sulfates. Specificity of the procedure for detecting heparin is further demonstrated by inhibition of labeling after preincubation with heparinase and by competition with exogenous heparin. On this basis, we conclude that heparin is present in essentially all mast cells in normal skin, lung alveolar wall, and bowel mucosa. The presence of heparin in all human mast cells is different than for rodent mast cells, and probably accounts for the inability to clearly distinguish different human mast cell types from one another with histochemical stains based on proteoglycan content.

Animals↗

PubMed1992

IL-3-dependent mast cells attach to plate-bound vitronectin. Demonstration of augmented proliferation in response to signals transduced via cell surface vitronectin receptors.

The adhesive interactions of activated mast cells with the extracellular matrix play an important role in anchorage and cellular motility. In this report we demonstrate that IL-3-dependent bone marrow-derived mast cells adhere to plate-bound vitronectin with high affinity in a saturable and dose-dependent manner. This adhesion interaction is unique in that it does not require prior mast cell activation through Fc epsilon RI or after treatment with PMA. It is inhibited by divalent cation chelation and by competitive inhibition with a synthetic Arginine-Glycine-Aspartate-Serine tetrapeptide. Polyclonal antisera for alpha v beta 3, an integrin known to bind vitronectin, inhibits attachment to plate-bound vitronectin in a dose-dependent manner. Comparison of the adhesion interactions for vitronectin, fibronectin, and laminin indicate that adhesion to vitronectin is greater than that seen with either fibronectin or laminin, either in the presence or absence of PMA. FACS analysis using a monoclonal hamster anti-murine vitronectin receptor (alpha v) antibody followed by a fluorescein-conjugated rabbit anti-hamster IgG revealed no change in surface vitronectin receptor expression after Fc epsilon RI-mediated cell activation. Proliferation assays with correction for cell viability revealed a 25% increase in cell number above the maximal IL-3 response over a 24-h period of adhesion to a vitronectin-coated surface and a 41% increase over 96 h of adhesion to vitronectin. Binding to plate-bound vitronectin was not able to sustain cell viability in the absence of IL-3. Thus, IL-3-dependent bone marrow-derived mast cells adhere to vitronectin, an extracellular matrix protein present throughout connective tissues. This interaction generates a signal that results in the augmentation of the maximal IL-3-dependent mast cell proliferative response, thus demonstrating at least one way in which the interaction between mast cells and extracellular matrix alter the biologic responsiveness of the mast cell.

Animals↗

PubMed1992

Food allergies.

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Digestive System↗

PubMed1992

Kinetics of the appearance of Fc epsilon RI-bearing cells in interleukin-3-dependent mouse bone marrow cultures: correlation with histamine content and mast cell maturation.

While it is known that mast cells arise from pluripotential hematopoietic cells and express their mature phenotypes in tissues, the sequence of events in maturation is incompletely understood. To study early mast cells, we sorted cells from interleukin-3 (IL-3)-dependent mouse bone marrow cultures on the basis of Fc epsilon RI and examined their morphology, histamine content, and growth characteristics. Flow cytometric analysis and sort showed that the Fc epsilon RI-bearing (Fc epsilon RI+) cells increased from 0% on day 0 to 90% by day 21 and that the total number of Fc epsilon RI+ cells increased from 0 at the start of culture to 3.75 x 10(5) cells by day 21 from an initial population of 1 x 10(5) cells. The dissociation rate of 125I-labeled IgE from early cultured cells resembled the dissociation rate of mouse IgE from mature murine mast cells. Mean fluorescence intensity increased over time, reflecting an increase in IgE receptor density. Fc epsilon RI+ cells were also positive for Fc gamma RII/III. Morphologic studies showed gradual acquisition of metachromatic granules in the Fc epsilon RI+ cells, which was paralleled by an increase in histamine content. Sorted Fc epsilon RI+ cells, when placed in liquid suspension culture, gave rise to pure mast cell populations. Fc epsilon RI+ cells sorted at day 3 and cultured in agarose with IL-3 gave rise to 4,800 small and 150 medium-size mast cell colony-forming units per 10(6) cells, while Fc epsilon RI- cells gave rise to 23 medium-size and 49 large mast cell colony-forming units per 10(6) cells. Fc epsilon RI+ cells grown in granulocyte-macrophage colony-stimulating factor (CSF) or macrophage-CSF did not give rise to colony-forming units. These results show that Fc epsilon RI+ cells have proliferative potential, but that there also is a population of mast cell progenitor cells that have not yet expressed Fc epsilon RI, and such individual progenitor cells have greater potential for proliferation than cells that express Fc epsilon RI.

Animals↗

PubMed1992

Effect of IL-3 and stem cell factor on the appearance of human basophils and mast cells from CD34+ pluripotent progenitor cells.

Hemopoietic stem cell factor (SCF), which is the ligand for the proto-oncogene c-kit receptor (allelic with W locus) and the product of Sl locus of the mouse, has recently been cloned. The human homologue has also been cloned, and recombinant protein (human rSCF) expressed and purified to homogeneity. To determine the effect of human rSCF in the presence or absence of human rIL-3 on human bone marrow-derived mast cells and basophils, human CD34+ pluripotent progenitor cells, highly enriched (greater than 99%) from bone marrow mononuclear cells, were cultured over agarose surfaces (interphase cultures) in the presence of human rIL-3, human rIL-3 and increasing concentrations of human rSCF, or human rSCF alone. Over 3 to 4 wk, human rSCF acted synergistically with human rIL-3 at all concentrations, producing a three- to fivefold increase in total, mast cell, and basophil numbers over human rIL-3 alone when used at 100 ng/ml. The percentage of cell types in the human rIL-3 and human rIL-3 plus human rSCF cultures, however, remained the same, with basophils constituting 18 to 35% of the final cultured cells, and mast cells 3% or less of the final cell number. In the presence of human rSCF alone, the combined total percentage of mast cells and basophils was 0 to 1.0%, the majority of cells being macrophages. Mast cells cultured in human rIL-3 plus human rSCF, but not human rIL-3 alone, were berberine sulfate positive, suggesting the presence of heparin proteoglycans within granules. Electron microscopic examination of cultures supplemented with human rIL-3 and rSCF, but not human rIL-3 alone, revealed that after 3 wk in culture, mast cell granules contained tryptase and exhibited scroll, reticular, and homogeneous patterns as seen previously in CD34+/3T3 fibroblast cocultures. Thus, CD34+ cells cultured in the presence of both human rIL-3 and rSCF give rise to cultures containing increased numbers of basophils and mast cells, with the mast cells by ultrastructural studies showing evidence of maturation although the percentages of basophils and mast cells arising in these cultures remained unchanged.

Basophils↗

PubMed1992

Passive cutaneous anaphylaxis in mouse skin is associated with local accumulation of interleukin-6 mRNA and immunoreactive interleukin-6 protein.

We used a BALB/c model of passive cutaneous anaphylaxis (PCA), an IgE-mediated, mast cell-dependent reaction, to demonstrate the early production of the proinflammatory cytokine interleukin-6 (IL-6) mRNA and protein product. Northern blot analysis detects IL-6 mRNA 1, and 2 hours after antigen challenge (dinitrophenyl30-40 human serum albumin [DNP30-40-HSA]) and in situ hybridization reveals that it is primarily cells with round-to-oval nuclei within the dermis (1 to 3 per high-power field) expressing IL-6 mRNA. Immunohistochemistry revealed perinuclear and cytoplasmic staining for immunoreactive IL-6 in mononuclear dermal cells and also cells within the basal keratinocyte layer. Injection of recombinant murine IL-6 (rmIL-6) either systemically or locally during antidinitrophenyl IgE skin sensitization resulted in increased vasopermeability at the PCA site after DNP30-40-HSA. However, this increased permeability was not associated with a change in the character of the cellular infiltrate at the PCA site 8 hours later. Although the specific role of IL-6 in the generation of the allergic response remains unknown, its detection during PCA unequivocally demonstrates that IL-6 be considered one of the mediators identified in inflammation that follows allergic reactions.

Animals↗

PubMed1992

Endothelins belong to the assortment of mast cell-derived and mast cell-bound cytokines.

Local accumulation of endothelins (ETs) as cytokine-like factors via autocrine/paracrine mechanisms seems to represent an important aspect of their pathophysiological action. This assumption prompted us to investigate mast cells as a possible source of these peptides. With the use of a combination of high-performance liquid chromatography and a radioimmunoassay specific for endothelin-1 (ET-1), 3-week-old cultures of primary murine bone marrow mast cells (BMMC) as well as various mast cell lines were shown to contain and secrete immunoreactive ET-1. The amounts of this peptide were constitutively high in cellular extracts of BMMC, while there was considerable variation in the basal cellular content among mast cell lines, ranging from high (C57) to undetectable (RBL) levels. Treatment of the cells with the combination of phorbol myristate acetate (PMA) and A23187 for 5 h led to induction of ET-1 production in all cases tested. In contrast to the rapid stimulation by PMA/A23187 of histamine release from BMMC or C57 cells, however, no ET-1 secretory response was noted as early as 30 min after this combined treatment. Moreover, stimulation of mast cells with crosslinked IgE for 30 min or 5 h did not affect ET-1 secretion, suggesting that mast cell ET-1 release is not directly related to mast cell degranulation. After exposure of the cells to crosslinked IgE for 20 h, however, there was a distinct increase in immunoreactive ET-1 in the medium, to approximate 10 times the basal level. Polymerase chain reaction (PCR) analysis of mRNA expression in mast cells revealed that the amount of ET-1 PCR product, which is low or undetectable under nonstimulated conditions, is enhanceable by both PMA/A23187 and crosslinked IgE. The IgE-mediated induction kinetics for ET-1 mRNA parallel the kinetics obtained with PMA/A23187, albeit at somewhat lower levels. With the use of fluorescent ligand binding/flow cytometry as a screening method and a radioreceptor assay as the confirming method, mast cells were found to express a single class of high affinity ET receptors with distinct selectivity for ET-1 and a pharmacological profile resembling that of the ETA type ET receptor. Stimulation of mast cell ET-1 receptors did not provoke histamine release, nor did it result in a mitogenic response of BMMC. In conclusion, mast cells synthesize and secrete ET-1 and have ET receptors, suggesting that ET-1 may participate in mediating mast cell-related long-term changes in the microenvironment, e.g., in smooth muscle tone or the proliferation rate of fibroblasts.

Animals↗

PubMed1992

Aphidicolin-induced proliferative arrest of murine mast cells: morphological and biochemical changes are not accompanied by alterations in cytokine gene induction.

Investigations of mast cell biology have often used immortalized cultured cells which are continuously proliferating. In vivo, however, only 2% or fewer tissue mast cells are actively dividing. We used aphidicolin, an inhibitor of DNA polymerase to induce a proliferative arrest of murine mast cells characterized by an inhibition of cell division and thymidine incorporation, with accumulation of cells in G1 and early S phase of the cell cycle. Uridine incorporation and cell viability were not significantly impaired. DNA synthesis and cell division both resumed rapidly upon removal of the drug. Morphometric analysis demonstrated that cell size, granule size, and number of granules per cell were all increased in aphidicolin-treated cells. Proliferative arrest also produced a 14-fold increase in cellular histamine content, but did not alter the proteoglycans synthesized by the cell. The level of c-myc mRNA was reduced in aphidicolin-arrested cells, but returned to the level observed in untreated cells within 1 hr of removal of the drug. In contrast, the constitutive steady-state RNA levels of tumour necrosis factor-alpha (TNF-alpha), B2-microglobulin, actin, and the c-Ha-ras and c-fes protooncogenes were not altered. Aphidicolin-induced proliferative arrest did not prevent the induction of TNF-alpha, interleukin-6 (IL-6) and c-fos genes in response to calcium ionophore. Both the magnitude and induction kinetics of these messages were similar in aphidicolin-treated and untreated cells. We conclude that proliferative arrest results in morphological and biochemical changes suggestive of cellular maturation, but inhibition of cell division alone is not sufficient to alter mast cell phenotype. Although optimal c-myc expression appears to require active proliferation, cytokine gene induction can occur in non-dividing cells. These data suggest that the proliferative quiescence of in vivo mast cells should not preclude their involvement in biological events via elaboration of multi-functional cytokines.

Actins↗

PubMed1991

Induction of mast cell proliferation, maturation, and heparin synthesis by the rat c-kit ligand, stem cell factor.

We investigated the effects of a newly recognized multifunctional growth factor, the c-kit ligand stem cell factor (SCF), on mouse mast cell proliferation and phenotype. Recombinant rat SCF164 (rrSCF164) induced the development of large numbers of dermal mast cells in normal mice in vivo. Many of these mast cells had features of "connective tissue-type mast cells" (CTMC), in that they were reactive both with the heparin-binding fluorescent dye berberine sulfate and with safranin. In vitro, rrSCF164 induced the proliferation of cloned interleukin 3 (IL-3)-dependent mouse mast cells and primary populations of IL-3-dependent, bone marrow-derived cultured mast cells (BMCMC), which represent immature mast cells, and purified peritoneal mast cells, which represent a type of mature CTMC. BMCMC maintained in rrSCF164 not only proliferated but also matured. Prior to exposure to rrSCF164, the BMCMC were alcian blue positive, safranin negative, and berberine sulfate negative; had a histamine content of 0.08 +/- 0.02 pg per cell; and incorporated [35S]sulfate into chondroitin sulfates. After 4 wk in rrSCF164, the BMCMC were predominantly safranin positive and berberine sulfate positive, had a histamine content of 2.23 +/- 0.39 pg per cell, and synthesized 35S-labeled proteoglycans that included substantial amounts (41-70%) of [35S]heparin. These findings identify SCF as a single cytokine that can induce immature, IL-3-dependent mast cells to mature and to acquire multiple characteristics of CTMC. These findings also directly demonstrate that SCF can regulate the development of a cellular lineage expressing c-kit through effects on both proliferation and maturation.

Animals↗

PubMed1991

Demonstration of the origin of human mast cells from CD34+ bone marrow progenitor cells.

It has been established that murine mast cells are derived from a pluripotent bone marrow stem cell. In humans, the corresponding pluripotent cell is included in the CD34+ bone marrow population. To determine whether human mast cells arise from CD34+ human progenitor cells, enriched CD34+ cells were cultured over agarose surfaces (interphase cultures) or cocultured with mouse 3T3 fibroblasts in the presence of recombinant human (rh) IL-3. The presence of both mast cells and basophils was determined using a variety of histochemical and immunohistologic techniques, including immunogold labeling for IgE receptors and mast cell tryptase. Mast cells and basophils continued to appear in cultures when T cell, B cell, macrophage, and eosinophil committed progenitor cells were removed, but were not seen in cultures from which CD34+ cells were removed. CD34+ cells layered over agarose in the presence of rhIL-3 were shown to give rise to cultures that contained mast cells (1 to 5%) and basophils (25 to 40%). Cultures supplemented with rhIL-4 showed no additional increase in mast cells or basophils. CD34+ cells cocultured with 3T3 fibroblasts in the presence of rhIL-3 gave rise to mast cells within the fibroblast monolayer, which by 6 wk comprised up to 46% of the monolayer. CD34-cells on 3T3 fibroblasts gave rise to few mast cells (2% of the monolayer). Mast cell granules from interphase cultures contained homogeneous electron-dense material. In contrast, mast cells within 3T3 monolayers at 6 wk contained a variety of granule morphologies, including scroll, mixed, reticular, dense core, or homogeneous patterns. We conclude that both human mast cells and basophils arise from CD34+ human progenitor cells.

Antigens, CD↗

PubMed1991

Hematologic manifestations of systemic mast cell disease: a prospective study of laboratory and morphologic features and their relation to prognosis.

PURPOSE: Systemic mast cell disease (SMCD) follows an indolent course in most patients, but a significant number of patients die of neoplastic hematologic disorders. Reviews of the literature and retrospective studies in a single institution have defined features that may be associated with a poor prognosis, but prospective studies have been lacking. Therefore, we prospectively analyzed the relationship between clinical, laboratory, and hematopathologic findings and clinical outcome in a series of 46 patients with mast cell disease. This analysis was employed to both define clinically useful prognostic variables and describe the histologic evolution of bone marrow mast cell infiltration and its relationship to hematologic neoplasia. PATIENTS AND METHODS: Forty-six adult patients were referred to the National Institutes of Health (NIH) with clinical and/or pathologic evidence of mast cell proliferation. All patients had bone marrow examinations, and 10 patients underwent serial bone marrow biopsies. The diagnosis of SMCD required pathologic documentation of bone marrow mast cell infiltrates. The patients were followed for up to 13 years at the NIH (up to 30 years after the initial pathologic diagnosis of mast cell disease). Statistical analysis defined the correlation between variables and the presence of diagnostic bone marrow lesions. The Kaplan-Meier method was used to construct survival curves, and the effects of various variables on the survival time were examined. RESULTS: Thirty-two of 46 patients (74%) had a bone marrow biopsy diagnostic for SMCD. The remaining 14 patients were considered to have cutaneous mast cell disease (CMCD). Univariate analysis showed that hepatosplenomegaly, alkaline phosphatase level, absolute lymphocyte count, and age at onset of symptoms were positively correlated with SMCD, whereas hemoglobin level was negatively associated with diagnostic bone marrow lesions. With multivariate analysis, only hemoglobin and absolute lymphocyte count remained as significant independent predictors of bone marrow findings. No CMCD patient died or had significant clinical deterioration in the 1- to 30-year period of follow-up (median = 8.5 years), whereas 10 of 32 SMCD patients (31%) died from 1 to 22 years after diagnosis (median = 2.5 years) (p less than 0.0001). Univariate analysis revealed the following variables as significantly increasing the risk of death in patients with SMCD: later onset of symptoms, absence of cutaneous mastocytosis, thrombocytopenia, elevated lactate dehydrogenase (LDH) level, anemia, bone marrow hypercellularity, qualitative peripheral blood smear abnormalities, elevated alkaline phosphatase level, and hepatosplenomegaly. Multivariate analysis showed that only the age at onset of symptoms and LDH levels were significant independent predictors of survival. Eight of the 10 SMCD patients who died had myeloproliferative or myelodysplastic syndromes or acute nonlymphocytic leukemia. CONCLUSION: Our prospective study has defined a number of important variables in patients with clinical evidence of mast cell proliferation that can predict both the presence of SMCD and the likelihood of fatal disease. Since recent evidence suggests that mast cells derive from a bone marrow hematopoietic progenitor, SMCD may represent a myeloproliferative condition with the propensity to evolve into a neoplastic granulocytic disorder in a significant minority of patients.

Adolescent↗

PubMed1991

A combined single-blind, double-blind, placebo-controlled study to determine the reproducibility of hypersensitivity reactions to aspartame.

Aspartame is an O-methyl ester composed of phenylalanine and aspartic acid. After its final approval as a sweetener in 1981, a number of reports of adverse reactions to aspartame appeared in the literature. To explore the pathogenesis of such reactions, we initiated a study in July 1986 to identify subjects with hypersensitivity reactions to aspartame with blinded challenge procedures. The study was closed after 32 months. During that time, we advertised in local newspapers and worked closely with the local community of allergists and dermatologists in an attempt to recruit subjects with hypersensitivity reactions to aspartame. A total of 61 self-referrals and physician referrals were screened, with 20 referrals evaluated in clinic. After this evaluation, 12 patients underwent single- and double-blind challenge with up to 2000 mg of aspartame. No subject with a clearly reproducible adverse reaction to aspartame was identified. In summary, we found that it is difficult to recruit study subjects with a history of hypersensitivity reactions to aspartame and that subjects who believed themselves allergic to aspartame did not have reproducible reactions.

Adult↗

PubMed1991

Food allergy.

Food allergy is now known to encompass a number of distinct clinical entities that follow the ingestion of specific food or food additives. Research continues to shed light on immediate reactions to foods and food protein-induced enterocolitis of newborns and infants. Adverse reactions to food additives remain an area of health concern. Studies of food allergies have entered an era in which improved clinical design is the hallmark of the research and conclusions may now be drawn reliably.

Adult↗

PubMed1991

Classification and diagnosis of mastocytosis: current status.

Mastocytosis is a disease characterized by an abnormal increase in mast cells. Manifestations of the disease are provoked in large part by the resultant increase in mast cell-derived mediators, which have a variety of local and systemic effects. Mastocytosis is variable in respect to the organ systems involved, clinical manifestations, and association with hematologic diseases. This has suggested the need for an improved classification scheme to allow assessment of prognosis and therapy. The heterogeneity of the disease patterns in mastocytosis strongly suggests that more than one biologic lesion may occur in the developmental sequence that leads to placement of mature mast cells in tissues.

Humans↗

PubMed1991

Pediatric mastocytosis.

The onset of mastocytosis occurs between birth and 2 years of age in approximately 55% of all cases; an additional 10% develop the disease before the age of 15 years. Mastocytosis in these age groups differs in many respects from mastocytosis that has its onset in adulthood. The typical presentation of pediatric-onset mastocytosis consists of cutaneous manifestations: either a solitary mastocytoma, urticaria pigmentosa, or, less commonly, diffuse cutaneous mastocytosis. Particularly in infants, bullous eruptions may occur. Mastocytosis in infants and children may involve internal organs, including the bone marrow and the gastrointestinal tract, although such manifestations appear to be less common in children than in adults. Plasma histamine levels may be elevated in pediatric-onset mastocytosis. Treatment usually involves the use of H1 and H2 antihistamines to control itching and to control the hypersecretion of gastric acid that may occur. The prognosis for children with mast cell disease is variable; approximately half of the children with urticaria pigmentosa may experience resolution of lesions and symptoms by adolescence.

Adolescent↗

PubMed1991

The liver, spleen, and lymph nodes in mastocytosis.

In systemic mastocytosis the liver, spleen, and lymph nodes may be infiltrated by mast cells, with patterns of infiltration specific for each tissue. This may result in hepatosplenomegaly and enlarged lymph nodes. Extensive involvement with mast cells may also be associated with organ dysfunction. Specifically, in the case of liver, mast cell infiltration may result in fibrosis, portal hypertension, and abdominal ascites. Clinically significant involvement of the liver, spleen, and lymph nodes appears to be more common in patients with aggressive forms of mastocytosis, including those with a hematologic disorder.

Humans↗