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Anaphylaxis to calcitonin.

BACKGROUND: The calcitonin is an hormone produced by the thyroid gland C cells. The salmon calcitonin is used in some osteomuscular diseases. There are few references of allergic reaction to this hormone. We introduce a case of a sixty years old woman with several previous episodes of rhinitis, conjunctivitis and perspiration immediately after the administration of salmon calcitonin with nasal spray or intramuscular administration (Calsynar). There were some temporal periods of good tolerance between these episodes. METHODS: Skin prick test (SPT), nasal and intramuscular challenge test with commercial salmon calcitonin (Miacalcic) were performed. Leukocyte histamine release test with salmon calcitonin and serum tryptase levels at baseline and after intramuscular challenge test were performed. RESULTS: The patient skin prick test with commercial calcitonin (Miacalcic. 50 UI/ml) was positive and negative in controls. The nasal challenge test with a calcitonin nasal spray, up to 150 UI, was negative. The intramuscular challenge test with 25 UI of Miacalcic was positive with an immediate anaphylactic reaction. Whole blood histamine release studies were negative. Serum tryptase levels after intramuscular challenge did not increase significantly with regard to the basal levels. CONCLUSION: We have introduced a case of anaphylaxis by calcitonin that suggest an IgE mediated hypersensitivity reaction.

Anaphylaxis↗

Fine structure of healthy human gingival mast cells and their immunological characterization.

Despite the great number of studies on mast cell population, at the present time few are the studies regarding the structural aspects of mast cells in human gingiva. In order to identify and characterize gingival mast cells, specimens of healthy human gingival tissue have been studied. Subsequently, in order to test mast cell capability of express TNF-alfa, samples of healthy gingiva with antibody anti-TNF-alfa have been incubated. The results showed that in human gingiva mast cells are numerous and ubiquitarious. These cells exhibit several morphological types of cytoplasmic granules with characteristic subgranular content, varying in shape and density. This allows to divide gingival mast cells into two different subpopulations: either cells containing granules with compact coiled scrolls and/or particles and cells showing granules with scrolls and thin parallel bands. The two ultrastructural aspects observed seem to be correlated to the McT (mast cells containing tryptase) and McTC (mast cells containing tryptase and chymase) described in international literature, differing for ultrastructural aspect, biochemical content and response to secretagogue substances. The positivity of the reaction for TNF-alfa seems indeed to confirm that gingival mast cells are able to secrete sensible amounts of TNF-alfa.

Adolescent↗

[Effect of loratadine in children with allergic rhinitis].

The authors examined 25 children with allergic rhinitis, who were sensitive to grass, weed and tree pollens. During the allergic season nasal lavage was performed then repeated after 4 weeks of loratadine treatment. Tryptase, IL-5, ECP, TNF-alpha and RANTES levels were measured from the nasal lavage fluid. Tryptase, IL-5, and ECP levels were decreased significantly while the decrease of RANTES and TNF-alpha levels was not significant. The authors emphasize that loratadine is an effective anti-inflammatory drug which affects the early and late phase of immediate hypersensitivity. In the moderate cases loratadine is enough to relieve the symptoms, while in the severe forms anti-allergic eye drops and nasal antihistamine or steroid spray has to be added.

Adolescent↗

Preliminary evaluation of mast cells in rats with an experimental fibrosarcoma induced by 3-methylcholanthrene.

The aim of the study was the evaluation of mast cells in experimental fibrosarcoma induced in the rats' skin. Experiments were carried out on 50 male Wistar rats divided into three groups: 1. The cancer was induced in 34 rats' by onefold subcutaneous injection of 0.2 mg 3-methylcholanthrene in 0. 25 ml of olive oil; 2.--8 rats received subcutaneous injection of 0.25 ml olive oil; and 3.--8 rats, no treatment. The tumors developed after 14-35 weeks. The examined tumors had the mass of 1 g to 176 g--mean 15 g. Tissue material was fixed in Carnoy's or Bouin's fluid. Paraffin sections were stained with hematoxylin and eosin and using Azan methods. Mast cells were stained with alcjan blue+saphranin and with toluidine blue in pH 1.5. Immunohistochemical reactions detecting tryptase in mast cells and von Willebrand Factor in endothelial cells were also performed--using specific antibodies (DAKO) and ABC complex. We have found a very significant growth of the quantity of mast cells in the connective tissue of tumours. The distinct increase in immunostaining was found for tryptase in mast cells of the tumor periphery zone, where most areas of strong neoangiogenesis were found.

Animals↗

Quantitative analysis of interstitial mast cells in lupus and non-lupus membranous glomerulopathy.

Eleven renal biopsy specimens from patients with lupus membranous glomerulopathy (LMGN) and 16 from patients with primary (nonlupus) membranous glomerulopathy (NLMGN) for whom light, electron microscopy and immunofluorescence microscopy, and full clinical data were available were examined quantitatively. As a control 10 biopsy specimens of the kidneys removed because of trauma were used. Morphometric investigations were performed by means of a computer image analysis system to evaluate whether mast cells have a role in tubulointerstitial fibrosis in lupus and nonlupus membranous glomerulopathy and to examine the relationship between mast cells and interstitial alpha-smooth muscle actin (alpha-SMA) expression as well as interstitial infiltrates. The morphometric study revealed that the mean values of interstitial tryptase positive cells, expression of alpha-SMA, interstitial volume, CD68+, CD45RB+, CD43+ and CD20+ cells were significantly increased in LMGN as compared with NLMGN. In both LMGN and NLMGN groups there were significant positive correlations between interstitial tryptase positive cells and interstitial expression of alpha-SMA, interstitial volume, serum creatinine as well as CD68+ cells. The present data suggest that in cases of membranous glomerulopathy with a large number of interstitial mast cells systemic lupus erythematosus should be taken into consideration, even if this aetiology was not clinically suggested at the time of biopsy. Additionally, in both LMGN and NLMGN significant positive correlations between interstitial mast cell count and relative interstitial volume support the role of these cells in the development of interstitial fibrosis, however this relationship needs further investigations.

Adult↗

Effect of fexofenadine, a mast cell blocker, in infertile men with significantly increased testicular mast cells.

AIM: To investigate the role of fexofenadine, a mast cell blocker, on semen quality in the treatment of infertile men. METHODS: The study included 16 Turkish idiopathic infertile men with azoospermia or oligozoospermia who underwent testicular biopsy to examine mast cells containing tryptase. In all patients, a complete medical history, clinical examination, semen analysis and serum hormone assay were carried out. The biopsy specimens were immunohistochemically stained with antihuman tryptase for mast cells. The number of total mast cells per seminiferous tubule was calculated and recorded as mast cell index. The patients were divided into two groups according to their mast cell index: the higher (> or =1, n=9) and the lower (<1, n=7) index groups. Fexofenadine was administered orally at a dose of 180 mg/day for 4 to 9 months. Pre- and post-treatment semen parameters, including total motile sperm counts (TMC) were recorded and compared. Spontaneous pregnancies after the treatment were registered. RESULTS: There was no statistically significant difference in TMC between the pre-treatment and post-treatment values in patients with higher and lower mast cell index (P> or =0.05). In both groups, nobody had a significant response to the treatment and there was no spontaneous pregnancy after the treatment. CONCLUSION: Although testicular dysfunction is closely associated with increased number of testicular mast cells, fexofenadine, a mast cell blocker, appears not having any benefit in the treatment of Turkish infertile men with a significant increase in testicular mast cells.

Adult↗

[The pathogenesis of vitreoretinal diseases from the standpoint of molecular biology].

It is important to study the pathogenesis in vitreoretinal diseases to develop new medical therapy. We investigated the molecular mechanisms underlying the genesis of idiopathic macular hole, exudative age-related macular degeneration (AMD), and diabetic retinopathy. We observed high levels of chymase and tryptase activity in the vitreous humor of patients with idiopathic macular hole. This activity was significantly higher than in other vitreoretinal diseases. Immunohistochemical study using monkey eyes showed the possibility that Müller cells in foveal lesions have properties similar to retinal stem cells. Intravitreal injection of chymase induced apoptosis of foveal retinal cells and fibrous change of vitreoretinal interface in the macular area. Biochemical study using cultured human Müller cells revealed that chymase caused the inhibition of growth and the induction of apoptosis in dedifferentiated Müller cells treated with basic fibroblast growth factor (bFGF). These findings show that increased production of chymase and tryptase in mast cells could be related to the pathogenesis of idiopathic macular hole. Oxidative stress and arterosclerosis may be the major causes of exudative AMD. Paraoxonase (PON) is a polymorphic protein known to prevent oxidation of low-density lipoprotein (LDL). We analyzed PON genotypes and found that two types of polymorphism were significantly different between patients with AMD and control subjects. We also investigated serum oxidized low-density lipoprotein(oxLDL) levels, PON activity, and extracellular superoxide dismutase(EC-SOD) levels. All these factors were significantly higher in patients with AMD than in controls. Titers of IgA and IgG antibodies against chlamydia pneumoniae in the serum of AMD patients were also significantly higher than in controls. These results indicate that genetic factors related to PON polymorphisms, vascular damage caused by increment of serum oxLDL and malfunction of EC-SOD, and chronic inflammation provoked by clamydia pneumoniae infection may be involved in the pathogenesis of AMD. Excess accumulation of advanced glycation end products(AGEs) has a causative role in the development of diabetic complications. We determined the concentrations of three AGEs (pentosidine, carboxy-methyllysine, and crossline) and two cytokines (VEGF, IL-6) using ELISA. The levels of the three AGEs and two cytokines in the vitreous of patients with proliferative diabetic retinopathy(PDR) were significantly higher than in controls. The concentrations of VEGF and IL-6 were strongly correlated with the level of these AGEs. Cultured human Müller cells expressed both VEGF and IL-6 mRNA and these expressions were augmented after the treatment of AGEs, while also acting as photosensitizers and accelerating the degradation of hyaluronic acid in vitro. AGEs may consequently play an important role in the pathogenesis of diabetic retinopathy by inducing the production of VEGF and IL-6 in retinal Müller cells and the acceleration of vitreous liquefaction.

Animals↗

Immunohistochemical analysis of the interstitial mast cells in rebiopsied patients with idiopathic mesangial proliferative glomerulonephritis.

Recent evidence suggests a role for mast cells in the pathogenesis of renal scarring in various glomerulopathies, therefore the present study was undertaken to evaluate whether mast cells have a role in tubulointerstitial fibrosis in rebiopsied patients with idiopathic mesangial proliferative glomerulonephritis (MPG) and to examine a possible relationship between mast cells and interstitial alpha-smooth muscle actin (alpha-SMA) expression as well as interstitial infiltrates. Seventeen patients with idiopathic mesangial proliferative glomerulonephritis, in whom renal biopsies were repeated and for whom light and electron microscopy as well as immunofluorescence microscopy and full clinical data were available were examined quantitatively. Morphometric investigations were performed by means of a computer image analysis system. The study revealed that at the rebiopsy proteinuria was significantly lower as compared with the first biopsy. On the other hand, the mean values of the interstitial tryptase positive cells, expression of alpha-SMA, interstitial volume and CD68+ cells were at rebiopsy significantly increased. The mean values of CD45RB+, CD43+ and CD20+ cells did not differ significantly in these groups. In both initial biopsy and rebiopsy groups there were significant positive correlations between interstitial tryptase positive cells and interstitial expression of alpha-SMA, interstitial volume, and CD68+ cells. The present quantitative study may suggest that despite of the clinical improvement at rebiopsy, MPG is a progressive glomerular disease, and point to a role of mast cells in this process.

Actins↗

Isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial Clara cells. A possible activator of the viral fusion glycoprotein.

A novel trypsin-like protease associated with rat bronchiolar epithelial Clara cells, named Tryptase Clara, was purified to homogeneity from rat lung by a series of standard chromatographic procedures. The enzyme has apparent molecular masses of 180 +/- 16 kDa on gel filtration and 30 +/- 1.5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Its isoelectric point is pH 4.75. Studies with model peptide substrates showed that the enzyme preferentially recognizes a single arginine cleavage site, cleaving Boc-Gln-Ala-Arg-4-methylcoumaryl-7-amide most efficiently and having a pH optimum of 7.5 with this substrate. The enzyme is strongly inhibited by aprotinin, diisopropylfluorophosphate, antipain, leupeptin, and Kunitz-type soybean trypsin inhibitor, but inhibited only slightly by Bowman-Birk soybean trypsin inhibitor, benzamidine, and alpha 1-antitrypsin. Immunohistochemical studies indicated that the enzyme is located exclusively in the bronchiolar epithelial Clara cells and colocalized with surfactant. An immunoreactive protein with a molecular mass of 28.5 kDa was also detected in airway secretions by Western blotting analyses, suggesting that the 30-kDa protease in Clara cells is processed before or after its secretion. Proteolytic cleavage of the hemagglutinin of influenza virus is a prerequisite for the virus to become infectious. Tryptase Clara was shown to cleave the hemagglutinin and activate infectivity of influenza A virus in a dose-dependent way. These results suggest that the enzyme is a possible activator of inactive viral fusion glycoprotein in the respiratory tract and thus responsible for pneumopathogenicity of the virus.

Amino Acid Sequence↗

Effect of Astragalus membranaceus injection on the activity of the intestinal mucosal mast cells after hemorrhagic shock-reperfusion in rats.

BACKGROUND: The mechanism of mucosal damage induced by ischemia-reperfusion (IR) after hemorrhagic shock is complex; mast cells (MC) degranulation is associated with the mucosal damage. Astragalus membranaceus can protect intestinal mucosa against intestinal oxidative damage after hemorrhagic shock, and some antioxidant agents could prevent MC against degranulation. This study aimed to observe the effects of astragalus membranaceus injection on the activity of intestinal mucosal mast cells (IMMC) after hemorrhage shock-reperfusion in rats. METHODS: Thirty-two Wistar rats were randomly divided into the normal group, model group, low dosage group, (treated with Astragalus membranacaus injection, 10 g crude medication/kg) and high dosage group (treated with Astragalus membranacaus injection, 20 g crude medication/kg). The rat model of hemorrhagic shock-reperfusion was induced by hemorrhage for 60 minutes followed by 90 minutes of reperfusion. The animals were administrated with 3 ml of the test drug solution before reperfusion. At the end of study, intestinal pathology, ultrastructure of IMMC, and expression of tryptase were assayed. The levels of malondisldehyde (MDA), TNF-alpha, histamine, and superoxide dismutase (SOD) activity in intestine were detected, and the number of IMMC was counted. RESULTS: The Chiu's score of the rats in the model group was higher than in other groups (P < 0.01). The Chiu's score in the high dosage group was higher than that in the low dosage group (P < 0.05). Hemorrhage-reperfusion induced IMMC degranulation: Astragalus membranaceus injection attenuated this degranulation. Expression of tryptase and the number of IMMC in the model group increased compared with the other groups (P < 0.01) and was significantly reduced by the treatments of Astragalus membranaceus injection at both doses. There was no significant difference between the two treatment groups (P > 0.05). MDA content and concentration of TNF-alpha in the model group were higher than that in the other three groups (P < 0.05), and the concentration of TNF-alpha in the low dosage group was higher than that in the high dosage group (P < 0.05). SOD activity and the concentration of histamine in the model group were lower than the other three groups (P < 0.05). There was a negative correlation between the Chiu's score and the concentration of histamine and a positive correlation between the Chiu's score and the concentration of TNF-alpha and between the SOD activity and the concentration of histamine in the four groups (P < 0.05). CONCLUSION: Astragalus membranaceus injection may reduce the damage to small intestine mucosa by inhibiting the activated IMMC after hemorrhagic shock.

Animals↗

A novel membrane-bound serine esterase in human T4+ lymphocytes immunologically reactive with antibody inhibiting syncytia induced by HIV-1. Purification and characterization.

A novel membrane-bound serine esterase, named tryptase TL2, which is immunologically reactive with the antibody inhibiting induction of syncytia by human immunodeficiency virus-1 (HIV-1) (Hattori, T., Koito, A., Takatsuki, K., Kido, H., and Kutunuma, N. (1989) FEBS Lett., 248, 48-52), has been purified from a human T4+ lymphocyte clone. The enzyme has a molecular mass of 198 +/- 15 kDa, as judged by gel-permeation liquid chromatography, and is composed of two subunits of 32 kDa and four subunits of 28 kDa, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Studies with model peptide substrates showed that the enzyme preferentially recognized L-arginine and cleaved Boc-Gln-Gly-Arg-4-methyl-coumaryl-7-amide and Boc-Gln-Ala-Arg-4-methyl-coumaryl-7-amide with high efficiency at a pH optimum of 8.5. The enzyme was strongly inhibited by the envelope glycoprotein gp 120 of HIV-1, by synthetic peptides with the sequence GPGR in their center, which corresponds to the principal neutralizing epitope of the gp 120s of various HIV-1 strains, by Kunitz-type inhibitors with the sequence GPCR in their active site, such as trypstatin, HI30, and [Arg15, Glu52]aprotinin and by the microbial inhibitors leupeptin and antipain. Studies on the subcellular distribution of tryptase TL2, immunohistochemical analysis, and cell surface radioiodination indicated that the enzyme is mainly localized in the plasma membrane.

Blotting, Western↗

[Mast cell mediator release after endobronchial challenge with adenosine 5'-monophosphate in asthmatic subjects].

Mediator release from activated mast cells is also likely to take place in the asthmatic airways in vivo during adenosine-induced bronchoconstriction. To test this hypothesis, we evaluated mast cell mediator release directly into the airways of 9 asthmatic subjects after endobronchial challenge with adenosine by bronchoalveolar lavage (BAL). The mediators measured were histamine, tryptase, and PGD2. When compared to the saline-challenged segment, the response to AMP instillation was characterized by a prompt reduction in airway calibre paralleled by a significant 4.2-fold increase in PGD2 levels in the BAL fluid (p = 0.004). There were also increases in median histamine (from 200.1 to 433.6 pg/mL) and tryptase levels (from 0.31 to 0.46 ng/mL) recovered after AMP challenge, although they were not significant. These findings support the view that acute bronchospastic response to AMP in asthmatic airways is paralleled by the local release of mast cells derived products, particularly PGD2.

Adenosine Monophosphate↗

Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/Fc epsilon RI- cell population.

Mast cells may be cultured from human peripheral blood in the presence of recombinant human stem cell factor (rhSCF). The characteristics of the cells in peripheral blood that give rise to mast cells are unknown. Because mast cell precursors in human marrow are CD34+, human peripheral blood mononuclear cells from patients with mastocytosis and normal controls were sorted on the basis of CD34 expression and the positive and negative cell populations were cultured in rhSCF, recombinant human interleukin-3 (rhIL-3), or both for 6 weeks. Cell cultures were examined every 2 weeks for total and mast cell number and cell differential using Wright Giemsa and acid toluidine blue stains and antibodies to mast cell tryptase and chymase, cell-associated histamine, and expression of CD34, c-kit, Fc epsilon RI, and Fc gamma RII using flow cytometric analysis. The ultrastructural anatomy of mast cells was examined by electron microscopy. Peripheral blood CD34+ cells cultured in rhSCF with or without rhIL-3 gave rise to cell cultures consisting of greater than 80% mast cells by 6 weeks. CD34+ cells cultured in rhIL-3 alone did not give rise to mast cells, whereas rhIL-3 plus rhSCF increased the final mast cell number eightfold when compared with cells cultured in rhSCF alone. Mast cells increased concomitantly with a decrease in large undifferentiated mononuclear cells. CD34- cells did not give rise to mast cells. Histamine content per cell at 6 weeks was approximately 5 pg. Electron microscopy of 4-week cultures showed immature mast cells containing predominantly tryptase-positive granules that were either homogeneous or contained lattice structures, partial scroll patterns, or central dense cores and mixtures of vesicles, fine granular material, and particles. The CD34+ population at day 0 expressed Kit (65%) and Fc gamma RII (95%), but not Fc epsilon RI, by fluorescence-activated cell sorter analysis. At 6 weeks, CD34+-derived mast cells exhibited Fc epsilon RI in addition to Kit and Fc gamma RII, and were negative for CD34 antigen. Patients with mastocytosis showed a higher number of mast cells per CD34+ cell cultured compared with normal controls. Thus, the mast cell precursor in human peripheral blood is CD34+/Fc epsilon RI- and gives rise to mast cells in the presence of rhSCF with or without rhIL-3, and the number of mast cells arising per CD34+ cell in culture is greater when the CD34+ cells are obtained from patients with mastocytosis compared with normal subjects.

Antigens, CD↗

Protein Fv produced during vital hepatitis is a novel activator of human basophils and mast cells.

Protein Fv is found in the normal liver and is released in the stools of patients suffering from viral hepatitis. Protein Fv isolated from five patients stimulated the release of histamine and sulfidopeptide leukotriene C4 from purified and unpurified peripheral blood basophils. Protein Fv absorbed with protein A-Sepharose coated with polyclonal IgG did not induce histamine secretion, whereas removal of putative contaminating Ig did not modify the releasing activity. The characteristics of the release reaction were similar to those of rabbit IgG anti-Fc fragment of human IgE (anti-IgE). There was an excellent correlation (Spearman rank coefficient (rs) = 0.83; p < 0.001) between the maximal percent histamine release induced by protein Fv and that induced by anti-IgE from basophils. Preincubation of basophils with either protein Fv or anti-IgE resulted in complete cross-desensitization to a subsequent challenge with heterologous stimulus. Basophils from which IgE had been dissociated by brief exposure to lactic acid no longer released histamine in response to anti-IgE and protein Fv. A monoclonal IgE purified from a myeloma patient (patient ADZ) blocked both anti-IgE- and protein Fv-induced releases, whereas human polyclonal IgG and a monoclonal IgG purified from another myeloma patient (patient ZEG) selectively blocked protein Fv-induced secretion. Protein Fv also induced the release of preformed (histamine and tryptase) and de novo synthesized mediators (sulfidopeptide leukotriene C4 and/or PGD2) from mast cells purified from human lung parenchyma and skin tissues. There was a significant correlation between the maximal percent histamine release induced by protein Fv and anti-IgE from skin mast cells (rs = 0.63; p < 0.01). There was also an excellent correlation between histamine and tryptase release caused by protein Fv from both lung (rs = 0.80; p < 0.001) and skin mast cells (rs = 0.70; p < 0.01). Thus, we established that protein Fv acts as a novel activator of human basophils and mast cells presumably by interacting with the VH domain of the IgE.

Animals↗

[Mechanism of hepatocarcinogenesis by hepatitis B virus].

The X gene product of hepatitis B virus (HBV) has a trans-activation function. The AP-1, AP-2, kappa B-like, and C/EBP-like sequences, and the 26-bp element in HBV enhancer were identified as X-responsive elements. Although the X protein possesses a transcriptional activation domain, it doesn't bind to the X-responsive elements. However, CREB/ATF-2 becomes able to bind to a CRE-related sequence in the 26-bp element once it complexes with X protein. In addition, X protein was shown to have amino acid sequences homologous to the essential domain of Kunitz-type serine protease inhibitors and directly interacted with the protease, tryptase TL2. Results suggest that X protein modulates the tryptase TL2 activity, which may be involved in the proteolytic cleavage of cellular transcription factors.

Amino Acid Sequence↗

[Allergic inflammatory markers in upper respiratory allergies].

The inflammatory mediators of allergy were investigated in symptomatic patients suffering from upper respiratory tract allergy. The serum tryptase level as an indicator of mast cell activation and serum eosinophil cationic protein level as an indicator of eosinophil activation were measured. They did not find any alteration in the serum level of tryptase. The level of eosinophil cationic protein significantly increased in symptomatic patients comparing to normal healthy controls. There was not any correlation to the severity of symptoms and to the absolute eosinophil count in the peripheral blood. The different activation possibilities of the eosinophil granulocytes are discussed, highlighting the role of Th2-helper lymphocytes.

Adult↗

Mast cells in loosening of totally replaced hips.

This study evaluated mast cells in tissue around loose total hip implants. Interface and pseudocapsular tissues were obtained from 6 patients with a loose hip prosthesis. Mast cells were labeled with monoclonal mouse antihuman antibodies against tryptase and chymase in avidin-biotin-peroxidase complex staining and were quantitated morphometrically by means of a semiautomatic Kontron image analyzer. Almost all mast cells in situ were chymase-positive and tryptase-positive connective tissue cells. The mean number of such cells per mm2 of tissue increased in this rank order: interface (9.98 +/- 5.03 cells) < pseudocapsule (15.85 +/- 4.99 cells) < control knee synovium (25.08 +/- 8.64 cells). Mast cells in periprosthetic tissue, in contrast to normal knee synovial tissue, exhibited granule release. Mast cells around loose hip prostheses appeared to be activated by connective tissue mast cells. These were found in diminished numbers and in a degranulated state in the interface tissue between implant and bone. Mast cell activation in loco may thus lead to significant local production and/or release of proinflammatory mast cell mediators. Prevention of mast cell activation (degranulation) could prove useful in the postponement of loosening of the totally replaced hip.

Aged↗

A case of malignant mastocytosis with circulating mast cell precursors: biologic and phenotypic characterization of the malignant clone.

The phenotypic and biologic properties of malignant cells in a case of aggressive mastocytosis with multi-organ involvement, circulating mast cell precursors and absence of skin infiltrates were analyzed. Circulating mast cell precursors were detected by immunostaining using antibodies against mast cell tryptase as well as by electron microscopy. These progenitors were tryptase+/chymase- (MCT) and accounted for 10 to 20% of nucleated mononuclear blood cells (MNC). A subset of them contained metachromatic granules. As assessed by combined toluidine blue/immunofluorescence staining, the granulated mast cell precursors were found to express CD9 (P24), CD33 (gp67) and CD44 (Pgp-1), but not basophil-related markers (CD11b (C3biR), CDw17 (lactosylceramide), CD123 (il-3R alpha))or monocyte-related antigens (CD14, CD15). Expression of the mast cell growth factor (MGF) receptor, c-kit(CD117), was also demonstrable, whereas the skin mast cell marker C5aR (CD88) could not be detected on mast cell precursors. The ligand of c-kit, recombinant human (rh) stem cell factor (SCF = MGF), induced histamine release from circulating mast cell progenitors, whereas rhC5a, a potent skin mast cell-/basophil-agonist, was ineffective over the dose-range (10(-9) to 10(-7(M)) tested. Analysis of mast cell antigens in malignant mastocytosis or mast cell leukemias may be helpful to establish a diagnosis and to determine the phenotype of the clone.

Adult↗