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PubMed1994

Growth in methylcellulose of human mast cells in hematopoietic colonies stimulated by steel factor, a c-kit ligand.

We examined the effect of Steel factor (SLF) on the development of human mast cells in hematopoietic colonies from cord blood mononuclear cells in methylcellulose culture. When cord blood cells were cultured for 3 weeks, SLF increased the cellular tryptase levels detected in total cultured cells. It also stimulated the formation of small-cell colonies consisting mainly of polymorphonuclear granulocytes and immature blastoid cells in a concentration-dependent manner but not the formation of colonies consisting of large macrophagic cells. A low percentage of tryptase-positive mast-cell-like cells was found in 39 out of 100 granulocyte/blastoid cell colonies. Four of the 100 colonies contained 10-20% tryptase-positive cells, but we failed to observe colonies consisting of > 20% of tryptase-positive cells. These results suggest that the effect of SLF on mast cell growth is brought on by stimulating the growth of primitive hematopoietic progenitors.

Cell Adhesion Molecules↗
PubMed2001

Synaptotagmin I expression in mast cells of normal human tissues, systemic mast cell disease, and a human mast cell leukemia cell line.

Synaptotagmin I (STG I) is a Ca(2+) sensor and one of the synaptic vesicle proteins that mediate exocytosis. To determine the mechanism of release of large granules from mast cells, we studied by immunohistochemistry the presence of STG I in mast cells in normal human tissues simultaneously with the mast cell markers mast cell tryptase (tryptase) and c-kit. The tumor cells of systemic mast cell disease (SMCD) and a human mast cell leukemia cell line (HMC-1) were also examined. Human mast cells in normal tissues and the tumor cells of SMCD expressed STG I as well as mast cell tryptase (tryptase) and c-kit. STG I mRNA and its products in HMC-1 were examined by RT-PCR analysis and immunocytochemistry, respectively. STG I expression in HMC-1 cells was compared with that in cells stimulated and non-stimulated by phorbol 12-myristate 13-acetate and also with that in NB-1 and PC12 cells, known to express STG I. STG I mRNA was detected in both non-stimulated and stimulated HMC-1 cells and in NB-1 and PC12 cells. STG I immunoreactivity was weaker than NB-1 or PC12 immunoreactivity. However, it increased in the stimulated HMC-1 cells. Mast cells expressed STG I in various states. STG I may mediate exocytosis of large granules in mast cells.

Biomarkers↗
PubMed2006

Pseudoanaphylaxis.

Profound hypotension and cardiac arrest after commencement of combined spinal and general anaesthesia in a patient for knee replacement surgery raised the suspicion of anaphylaxis. This seemed to be confirmed when a mast cell tryptase test taken about 90 minutes after the onset of the hypotension was elevated. However, subsequent intradermal skin testing twelve weeks later did not identify a causal drug. Repeat mast cell tryptase at the time showed the same elevation, which led to the correct diagnosis of mastocytosis and a secondary diagnosis that the patient's hypotension and cardiac arrest were the result of her spinal anaesthesia. If the serum tryptase is elevated during the event but no allergic agent can be identified, a further serum tryptase should be taken several weeks later to exclude a persistent elevation due to mastocytosis.

Anaphylaxis↗
PubMed2005

Physiology and pathophysiology of proteinase-activated receptors (PARs): role of tryptase/PAR-2 in vascular endothelial barrier function.

Proteinase-activated receptor-2 (PAR-2) plays important roles in a variety of pathophysiological functions, including inflammatory responses and nociception. In this minireview, we describe the role of PAR-2 in acute inflammatory responses in lungs associated with iodinated radiographic contrast medium (RCM). Intravenous injection of RCM to rats induces lung injury characterized by vascular hyperpermeability, edema, and respiratory depression. Nafamostat, which is found to be the most potent and specific tryptase inhibitor, prevents RCM-induced lung injury. In cultured endothelial cells of human pulmonary artery and bovine aorta, RCM, when applied in combination with mast cells, disrupts barrier function evaluated by the permeability of Evans blue through a monolayer of cultured cells, which is blocked by nafamostat and mimicked by tryptase and PAR-2-activating peptide. The tryptase-induced barrier dysfunction is blocked completely by a phospholipase C inhibitor and partially inhibited by a IP(3) receptor blocker, protein kinase C inhibitor, or Rho kinase inhibitor. Morphological observations reveal the formation of actin stress fibers and disappearance of the intercellular meshwork structure of vascular endothelial-cadherin after application of RCM or PAR-2 ligands. Therefore, the release of mast cell tryptase and subsequent activation of endothelial PAR-2 are involved in acute lung injury induced by RCM.

Animals↗
PubMed2005

Immunohistochemical and histochemical stains for differentiating canine cutaneous round cell tumors.

Immunohistochemical and histochemical stains are useful adjunct techniques in the diagnosis of canine cutaneous round cell tumors, which can appear histologically similar. We applied a panel of monoclonal antibodies (recognizing tryptase, chymase, serotonin for mast cells; CD1a, CD18, MHC class II for histiocytes; CD3 for T lymphocytes; CD79a for B lymphocytes and plasma cells) and one histochemical stain (naphthol AS-D chloroacetate for chymase activity) to formalin-fixed, paraffin-embedded sections of canine cutaneous mast cell tumors, histiocytomas, lymphosarcomas, plasmacytomas, and unidentified round cell tumors. Of 21 tumors with a histologic diagnosis of mast cell tumor, 7/7 (100%) grade I, 6/7 (85.7%) grade II, and 3/7 (42.9%) grade III tumors were diagnosed as mast cell tumors based on positive staining for tryptase antigen and chymase activity. Mast cells were positive for both tryptase antigen and chymase activity, indicating equal efficacy of tryptase immunohistochemistry and chymase histochemistry. Chymase was detected immunohistochemically in both tumor and nontumor cells, while serotonin was not detected in most mast cell tumors, and thus, neither was useful in the diagnosis of mast cell tumors. Immunohistochemistry to detect CD18 and MHC class II was equally effective in staining histiocytomas, although lymphosarcoma must be ruled out through the use of CD3 and CD79a immunohistochemistry. Immunohistochemistry using three different monoclonal antibodies to human CD1a showed no cross-reactivity in canine histiocytomas and was not useful. A final diagnosis was obtained for 4/5 (80%) of the unidentified tumors, indicating the usefulness of multiple stains in poorly differentiated round cell tumors.

Animals↗
PubMed2005

Immunosurveillance function of human mast cell?

Mast cell (MC) is so widely recognized as a critical effector in allergic disorders that it can be difficult to think of MC in any other context. Indeed, MCs are multifunctional and recently shown that MCs can also act as antigen presenters as well as effector elements of human immune system. First observations of their possible role as anti-tumor cells in peri- or intra-tumoral tissue were mentioned five decades ago and a high content of MCs is considered as a favorable prognosis, consistent with this study. Believers of this hypothesis assumed them to be inhibitors of tumor development through their pro-apoptotic and -necrolytic granules e.g., granzymes and TNF-alpha. However, some still postulate them to be enhancers of tumor development through their effects on angiogenesis due to mostly tryptase. There are also some data suggesting increased MC density causes tumor development and indicates bad prognosis. Furthermore, since MC-associated mediators have shown to influence various aspects of tumor biology, the net effect of MCs on the development/progression of tumors has been difficult to evaluate. For instance, chymase induces apoptosis in targets; yet, tryptase, another MC protease, is a well-known mitogen. MCs with these various enzyme expression patterns may mediate different functions and the predominant MC type in tissues may be determined by the environmental needs. The coexistence of tryptase-expressing MCs (MC(T)) and chymase and tryptase-expressing MCs (MC(TC)) in physiological conditions reflects a naturally occurring balance that contributes to tissue homeostasis. We have recently discussed the role and relevance of MC serine proteases in different bone marrow diseases.

Animals↗
PubMed2001

Accumulation, distribution and phenotype heterogeneity of mast cells (MC) in human brains with neurocysticercosis.

Neurocysticercosis (NCC) is one of the most common parasitic brain infections in the world NCC can cause widely varied clinical manifestations, mainly due to the host immune-inflammatory response. The immunological hallmark of the infection with helminth parasites is infiltration into the inflamed mucosa of the gastrointestinal tract of numerous mast cells. It has been postulated that mediators released by activated mast cells might contribute to the local inflammatory response. Since data concerning the association of mast cells with neurocysticercosis are not available, the aim of our study is to determine the distribution and phenotypes of mast cells in human brain infested by cysticerci. The study was performed on 20 human autopsy brains. Mast cells (MC) were identified by means of immunohistochemical method using specific MC tryptase and chymase monoclonal antibodies. In the control brains, mast cells were very few and showed a very sparse distribution. They had been occasionally found in meninges and in perivascular areas of some brain blood vessels. Those cells were mainly tryptase-chymase phenotype (MCTTC). In contrast, in the brain sections with neurocysticercosis, mast cells were numerous. A striking feature of identified mast cells was their phenotype heterogeneity. The tryptase mast cells (MCT) phenotype dominated over the tryptase-chymase (MCTC) phenotype. MCT infiltrated mainly meninges and brain parenchyma around cysts with viable and necrotic parasites. MCTC infiltrated perivascular area of the blood vessels penetrating to the depth of the brain. Summarising, this is the first report which documents the accumulation and phenotype heterogeneity of mast cells in human brains with neurocysticercosis. Our findings suggest that the effector mechanism responsible for the host responses to the parasitic infection that involves numerous mast cells in the human brain may be very important for pathomechanism of this disease.

Adolescent↗
PubMedDate not supplied

[Prospective epidemiologic study of perioperative anaphylactoid reactions occurring in Catalonia (1996-7)].

OBJECTIVES: To determine the incidence, immunological mechanisms, severity and clinical course of perioperative allergic reactions. PATIENTS AND METHODS: Prospective epidemiological study lasting 2 years (1996-97). In 20 hospitals in Catalonia (Spain), we studied patients who suffered allergic reactions equal to or greater than grade Ib according to the classification of Laxenaire. Serum and urine samples were collected during the first and sixth hours after the onset of a reaction. Complement factors, total serum and latex-specific serum IgE antibodies, hemostatic markers, serum tryptase and urinary methylhistamine were assayed. Tests for allergy to the drugs used during the perioperative period were performed on all patients who consented. RESULTS: Anesthetic procedures were performed 328,430 times in the 20 hospitals. Thirty-two allergic reactions were reported (1 case/10,263 anesthesias); the frequency was greater during general anesthesia (1 case/6,978 anesthesias). Women suffered 58.3% of the reactions, and the mean patient age was 47.8 +/- 16.5 years. Fifty-six percent of the reactions were severe (grades III-IV), and 68.7% occurred upon immediate exposure. Induction was the moment of greatest risk (50%). Treatment was required by 90.6% of the patients, but no deaths or serious sequelae occurred. Complete analyses could be carried out immediately for 25 patients. High urinary methylhistamine and/or serum tryptase levels were found for 57% of the patients with grade Ib reactions, for 80% of those with grade II reactions, and for 91.7% of those with grade III reactions (p = 0.05). High serum tryptase levels were the only findings for 53.8% of the grade III reactions (p = 0.007). Skin tests were positive for 62.5% of the patients. CONCLUSIONS: The frequency of allergic reactions in Catalonia is 1 case per 10,263 anesthesias performed, but the rate is higher in general anesthesia. Fifty-six percent of the reactions were severe. Most developed immediately and the moment of induction involved the greatest risk. Early assessment of methylhistamine and tryptase levels has been shown to be useful and positivity is linearly associated with severity of reaction. In 62.5% of the patients, positive results were seen in skin tests performed later.

Adolescent↗
PubMed2002

[Specific nasal provocative test in allergic rhinitis diagnosis: reliability and standardization].

Specific vasomotorial rhinopathy, or allergic rhinitis is to be seen as a systemic pathology characterized by a condition of hyperactivity, the target organ of which is the nose. Particular attention, among the diagnostic tests, should be reserved to the specific nasal provocative test (sNPT), which has been part of the clinical routine for years but has nonetheless failed to achieve a suitable level of standardization. With this intent, we have devoted the present work to the assay of several phlogosis mediators (tryptase, specific IgE and ECP) before and after performing the sNPT. We have studied 20 patients affected by allergic rhinitis, aged between 13 and 61, with single or multiple allergen sensitivities, but in any case with a predominant sensitization, who underwent sNPT between October 2000 and July 2001. In every patients we performed ECP, tryptase and specific IgE assay via direct incubation in the nasal mucosa, before and after specific nasal provocation. The results of the sNPT (rhinomanometry and symptoms score) were compared with the variations in the phlogosis mediators assayed at nasal level. On the basis of the variations in the rhinomanometric resistance and symptoms score, the sNPT was positive in 10 patients (50%). Tryptase and specific IgE increased to a statistically significant degree (respectively, p = 0.01 and p < 0.05) in all of the patients; the ECP variations, instead, were not significant (p > 0.05). Overall, the simultaneous assay of ECP, tryptase and specific IgE, increasing the sensibility of the sNPT, enabled a positive result to be ascertained in 60% of the subjects examined. The method is furthermore based on the principle of local reactivity in that it assays the phlogosis mediators not at systemic level, but directly in the target organ, showing itself to be more specific than level I and II tests.

Adolescent↗
PubMed1992

Human basophil/mast cell releasability. IX. Heterogeneity of the effects of opioids on mediator release.

Opioids differ in their capacity to cause release of histamine. The effects of increasing concentrations of three opioids (morphine, buprenorphine, and fentanyl) were studied on the release of preformed (histamine and tryptase) and de novo synthesized (prostaglandin D2 [PGD2] and peptide-leukotriene C4 [LTC4]) chemical mediators from human peripheral blood basophils and mast cells isolated from skin tissues or lung parenchyma. Basophils released < 5% of their histamine content and did not synthesize significant amounts of LTC4 when incubated with any of the opioids. Mast cells showed markedly different responses to the three opioids. Morphine (10(-5)-3 x 10(-4) M), in a concentration-dependent manner, induced histamine and tryptase release from skin but not from lung mast cells, up to a maximum of 18.2 +/- 1.9% and 13.0 +/- 4.1 micrograms/10(7) cells, respectively. Morphine did not induce de novo synthesis of PGD2 from skin mast cells. Buprenorphine (10(-6)-10(-4) M), in a concentration-dependent manner, caused histamine and tryptase release from lung but not from skin mast cells, to a maximum of 47.6 +/- 7.2% and 35.1 +/- 13.6 micrograms/10(7) cells, respectively. Buprenorphine also induced de novo synthesis of PGD2 and LTC4 from lung mast cells. Fentanyl (10(-5)-10(-3) M) did not induce histamine and tryptase release or the de novo synthesis of PGD2 or LTC4 from any mast cells. Histamine release caused by buprenorphine from lung mast cells was slow (t1/2 = 11.2 +/- 3.6 min) compared with that induced by morphine from skin mast cells (t1/2 < 1 min, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Basophils↗
PubMed1993

[Dermal reactions in children with atopic dermatitis--changes in histamine/tryptase levels in skin chambers. Report 1].

In the present study, we used the skin chamber method to determine histamine and tryptase released by continuous loading of a single antigen on the skin in order to evaluate dermal reactions produced and thereby obtain greater insight into the role of type I allergic reactions in children with atopic dermatitis. The subjects were 46 children, 23 males and 23 females aged 10.6 +/- 4.3 years on the average, who were being treated at the National Children's Hospital for moderate or severer atopic dermatitis. Mite antigen stimulation was carried out by the skin chamber method upon admission and histamine and tryptase levels in collected antigen solution were determined. Histamine levels in the chamber were increased significantly at 6, 12 and 24 hrs after stimulation compared to the control levels (p < 0.01). Tryptase levels were increased 2 hrs after stimulation but decreased with time thereafter. Histamine and tryptase levels were significantly correlated 2 hrs after stimulation, with a correlation coefficient of 0.954 (p < 0.01). No significant correlation was observed 24 hrs after stimulation. These findings indicate that children with severe atopic dermatitis have great skin reactivity and very sensitive to stimulation by antigens. Mast cells and basophils are thought to be involved in immediate and delayed type reactions, respectively.

Adolescent↗
PubMed1994

[Release of chemical mediators in the conjunctival lavage fluids after eye provocation with allergen or compound 48/80].

Allergen extract was used to perform conjunctival provocation test on patients with Japanese cedar pollen conjunctivitis during the off-season, and histamine, tryptase and immunoreactive-leukotriene C4 (i-LTC4), which mainly consisted of LTE4, were measured in the lavage fluids. The results obtained in this study were as following. 1) After instillation of the allergen extract (1:20, w/v, 0.01 ml), histamine reached a maximal level of 4.63 +/- 1.67 ng/ml (mean +/- SE, n = 11) at 5 min. Tryptase appeared more slowly and the peak levels were reached at 5 min (116.6 +/- 49.6 ng/ml) or 10 min (119.4 +/- 63.8 ng/ml). In another set of the experiments, histamine peaked at 5 min (3.84 +/- 1.08 ng/ml, n = 7), and i-LTC4 reached peaks at 5 min (320 +/- 44.4 pg/ml) or 10 min (367 +/- 64.8 pg/ml). The amounts of these mediators decreased to base-line levels by 30 min. 2) The amounts of histamine retrieved from the lavage fluid were significantly correlated with those of tryptase (r = 0.819, p < 0.01, n = 11) and the weight ratio of tryptase to histamine was 41.2 +/- 10.0. These observations suggest that histamine was released from mast cells. 3) A significant correlation between the levels of histamine and i-LTC4 recovered from the lavage fluids was also observed (r = 0.736, p < 0.05, n = 7). 4) Compound 48/80 was instilled in the right eye (7.5 mg/ml, 0.01 ml) and the left eye was given allergen solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1993

Cysteinyl leukotrienes overproduction and mast cell activation in aspirin-provoked bronchospasm in asthma.

In order to examine the hypothesis that in aspirin-induced asthma (AIA) cyclooxygenase inhibition is associated with enhanced release of leukotrienes (LTs), we measured urinary leukotriene E4 (LTE4) and 11-dehydro-thromboxane B2 (TXB2) (as a measure of cyclooxygenase production) following challenge with oral aspirin or inhaled methacholine, in 10 AIA patients. We also determined serum tryptase and eosinophilic catonic protein (ECP) levels, in order to evaluate mast cell and eosinophil activation. Urinary LTE4 excretion was increased sevenfold 4-6 h after aspirin challenge, while 11-dehydro-TXB2 decreased gradually reaching 50% baseline levels 24 h after challenge (p < 0.05). This was accompanied by a significant fall in blood eosinophil count at 6 h, and a tendency to a rise in ECP. The intensity of both LTE4 and 11-dehydro-TXB2 responses depended on the dose of aspirin used (p < 0.001, analysis of variance (ANOVA)). The accompanying maximum fall in forced expiratory volume in one second (FEV1) was not correlated with peak LTE4 levels. In contrast to aspirin, methacholine challenge producing comparable bronchial obstruction, did not alter eicosanoid excretion or serum tryptase or ECP levels. In a separate study, lysine-aspirin inhalation challenge was performed in seven AIA patients, four of whom had responded with a rise in serum tryptase to oral aspirin challenge. Challenge with inhaled aspirin led to similar bronchoconstriction as with oral challenge, but non-respiratory symptoms such as scarlet flush or rhinorrhea were absent, and serum tryptase levels remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Effects of nerve growth factor (NGF) and other fibroblast-derived growth factors on immature human mast cells (HMC-1).

We have previously shown that fibroblast and keratinocyte supernatants up-regulate expression of mast cell characteristics in the human immature mast cell line HMC-1. This effect could not be induced in HMC-1 cells by the well-known mast cell growth factor stem cell factor (SCF), probably due to mutations of the SCF receptor c-Kit in these cells. Here we report the effects of several known fibroblast- and keratinocyte-derived growth factors, namely nerve growth factor (NGF), basic fibroblast growth factor, platelet-derived growth factor and transforming growth factor-beta, on mast cell differentiation, using HMC-1 cells as a model. NGF, at 0.1-50 ng/ml concentrations, caused a marked, dose-dependent up-regulation of tryptase, Fc epsilon RI and histamine within 10 days of culture, associated with an enhanced expression of mRNA for Fc epsilon RI and mast cell tryptase. On restriction analysis, only mast cell beta-tryptase, but not alpha-tryptase, could be demonstrated. Furthermore, the high-affinity NGF receptor (TrkA) was found at both the transcriptional and protein levels, while expression of the low-affinity NGF receptor was detectable at the mRNA level only. None of the other growth factors caused a significant alteration of the mast cell markers studied when added to HMC-1 cells at concentrations known to be biologically active in other culture systems. Immature human mast cells are thus induced to assume a more mature phenotype in vitro in response to NGF, most probably via stimulation of the high-affinity NGF receptor expressed on these cells. Besides SCF, NGF should therefore be considered as an additional mast cell growth factor that contributes to human mast cell maturation at tissue sites.

Biomarkers↗
PubMed2006

Effect of nasal antifungal therapy on nasal cell activation markers in chronic rhinosinusitis.

OBJECTIVE: To examine the effect of nasal antifungal treatment on eosinophil cationic protein (ECP) and tryptase levels in samples of nasal lavage fluid from patients with chronic rhinosinusitis and nasal polyps. DESIGN: Prospective double-blind placebo-controlled clinical trial. SETTING: Tertiary surgical center. PATIENTS: Subjects with severe chronic rhinosinusitis and nasal polyps. Of 120 screened patients, 76 were eligible. Six patients withdrew because of minor adverse events, and 10 dropped out for other reasons. In total, 60 patients completed the study according to the study protocol. INTERVENTIONS: Nasal treatment with amphotericin B or saline control for 8 weeks. MAIN OUTCOME MEASURES: Nasal lavages were performed before and after treatment. Fungal elements were assessed by culture and with different polymerase chain reaction assays. Levels of ECP and tryptase were determined by fluorescent enzyme immunoassay. RESULTS: No correlation between cell activation markers and fungus detection was observed before treatment (all P>.20). Nasal amphotericin B treatment had no effect on levels of ECP (P = .17) or tryptase (P = .09) in nasal lavage samples. Moreover, successful fungus eradication, defined as fungus detection before but not after treatment, did not influence nasal ECP or tryptase levels (all P>.40). CONCLUSION: Neither topical amphotericin B therapy nor fungal state before and after treatment had any significant influence on activation markers of nasal inflammatory cells in chronic rhinosinusitis.

Administration, Intranasal↗
PubMed1992

Mast cell changes in scleroderma. Presence of MCT cells in the skin and evidence of mast cell activation.

OBJECTIVE: To analyze the concentration and distribution of the MCT (tryptase-positive, chymase-negative) and MCTC (tryptase-positive, chymase-positive) types of mast cell in cutaneous lesions of scleroderma. METHODS: Biopsy specimens were obtained from skin lesions in 24 patients with scleroderma, and subjected to double immunohistochemical analysis using mouse monoclonal anti-tryptase and anti-chymase antibodies. RESULTS: Dermal mast cell concentrations were below the normal range in 12 of the specimens, most of which were obtained between 1 and 4 years after disease onset. All other specimens contained normal concentrations of mast cells. MCT cells were present in 12 specimens and comprised between 8% and 100% of the total mast cells. Extracellular tissue deposits of tryptase-positive and/or chymase-positive granular material were observed in 8 specimens, suggesting possible mast cell degranulation. CONCLUSION: These findings are in contrast to those in normal skin, where MCTC cells are essentially the only type of mast cell present in the dermis. The results suggest that mast cells are involved in the pathogenesis of cutaneous lesions in scleroderma.

Adult↗
PubMed1996

Contrast media are incomplete secretagogues acting on human basophils and mast cells isolated from heart and lung, but not skin tissue.

To investigate the mechanisms of anaphylactoid reactions to radiocontrast media, in vitro mediator release induced by three iodinated contrast agents was examined using peripheral blood basophils and mast cells purified from human lung parenchyma, heart, and skin tissues. Three iodinated contrast agents, sodium and meglumine salts of ioxaglic acid, sodium and meglumine salts of ioxithalamic acid, and ioversol, were incubated with basophils purified from peripheral blood and human mast cells isolated and purified from different anatomical sites. Release of preformed (histamine and tryptase) and de novo synthesized mediators (prostaglandin D2 and leukotriene C4) into the supernatans was determined at various contrast medium concentrations after incubation for 60 min. Ioxaglate (0.2-0.3 M), ioxithalamate (0.3-0.5 M), and to a lesser extent ioversol (0.3-0.5 M) induced histamine release from basophils in a concentration-dependent manner. All three induced the release of preformed mediators (histamine and tryptase) from human lung, but not from skin mast cells. They also induced histamine and tryptase release from human heart mast cells. However, they did not induce the de novo synthesis of leukotriene C1 or prostaglandin D2 from human basophils or any type of mast cell examined. Cross-linking of IgE by anti-IgE induced the release of leukotriene C4 or prostaglandin D2 from human basophils or mast cells. Mannitol, an osmotic stimulus, induced the release of histamine from human basophils, but to a lesser extent from mast cells. These results show that different contrast media can differ in their ability to release mediators from enriched preparations of human basophils and mast cells. The three contrast agents examined act on basophils and mast cells as incomplete secretagogues, causing the release of preformed mediators, but not these novo synthesis of chemical mediators. It may be useful to measure plasma tryptase levels to detect adverse reactions caused by iodinated radiographic contrast materials.

Adult↗
PubMed2000

Effects of interferon-alpha2b treatment on ex vivo differentiation of mast cells from circulating progenitor cells in a patient with systemic mastocytosis.

Interferon (IFN)-alpha, a known inhibitor of myelopoiesis, is increasingly used to treat patients with systemic mastocytosis (SM). However, the mechanisms of IFN-alpha effects on mast cell (MC) growth remain unknown, and the treatment responses may be variable. In the present study, factor-dependent ex-vivo differentiation of MCs from peripheral blood mononuclear cells (PBMNCs) was analyzed in a patient with SM treated with IFN-alpha2b (3 million U/day). The patient exhibited an extensive MC infiltration in his bone marrow (BM) and increasing serum total tryptase levels (spiking to > 1,400 ng/ml). PBMNCs were collected before and during IFN-alpha2b treatment and cultured in the presence or absence of stem cell factor (SCF, 100 ng/ml) for 42 days. In the absence of SCF, no MC growth was detectable. However, in the presence of SCF, MC containing tryptase appeared in the cultures. Treatment with IFN-alpha2b resulted in a time-dependent decrease in SCF-inducible formation of MCs from PB progenitor cells in vitro. Also, during IFN-alpha2b treatment, blood histamine concentrations decreased. Serum total tryptase levels initially increased despite IFN-alpha2b treatment. However, after a latency period of a few months, tryptase concentrations declined and then reached a plateau. In healthy individuals, the SCF-induced in vitro growth of MCs from their progenitor cells was also inhibitable by the addition of IFN-alpha2b. In summary, our data show that IFN-alpha2b can exhibit inhibitory effects on factor-dependent growth of MC progenitor cells. However, it still remains open which of the patients with mastocytosis can benefit from long-term IFN-alpha treatment.

Adult↗