Difference In Number Of Mast Cells Research Articles

STAT5b dimers and tetramers are critical for Mast Cell Function

Abstract Signal transducers and activators of transcription (STATs) are latent transcription factors vital for lymphoid, myeloid, and erythroid cell development, survival, proliferation, and function. Activated STATs form dimers that translocate to the nucleus and bind high affinity STAT DNA motifs to modulate gene expression. We previously found that Stat5b is required for IgE-mediated mast cell cytokine production in vitro. In this study, we found that STAT5b KO mice demonstrate decreased sensitivity to IgE-mediated passive systemic anaphylaxis (PSA) and reduced cytokine production in vivo. This is not due to differences in mast cell numbers or distribution. Interestingly, STAT5b KO mice exhibit elevated levels of serum IgE that could diminish PSA by preventing binding of antigen-specific IgE. Increased serum IgE is not tied to changes in B cell number or their ability to produce IgE in vitro. In addition to dimers, activated STAT proteins can also form tetramers through an oligomerization process once dimers bind to tandem low-affinity STAT DNA motifs. Similar to STAT5bKO, in vitro IgE-mediated cytokine production is decreased in Stat5a-Stat5b double knock-in (DKI) mice in which STAT5 proteins can form dimers but not tetramers. In vivo, DKI mice exhibit decreased PSA sensitivity, with no difference in mast cell numbers or distribution, and a modest increase in serum IgE. Collectively, these data illuminate the unique and specific roles of STAT5 dimers and tetramers in mast cell function and allergic disease.

Transcription factor E3, a major regulator of mast cell–mediated allergic response

Microphthalmia transcription factor, an MiT transcription family member closely related to transcription factor E3 (TFE3), is essential for mast cell development and survival. TFE3 was previously reported to play a role in the functions of B and T cells; however, its role in mast cells has not yet been explored. We sought to explore the role played by TFE3 in mast cell function. Mast cell numbers were evaluated by using toluidine blue staining. FACS analysis was used to determine percentages of Kit and FcεRI double-positive cells in the peritoneum of wild-type (WT) and TFE3 knockout (TFE3(-/-)) mice. Cytokine and inflammatory mediator secretion were measured in immunologically activated cultured mast cells derived from either knockout or WT mice. In vivo plasma histamine levels were measured after immunologic triggering of these mice. No significant differences in mast cell numbers between WT and TFE3(-/-) mice were observed in the peritoneum, lung, and skin. However, TFE3(-/-) mice showed a marked decrease in the number of Kit(+) and FcεRI(+) peritoneal and cultured mast cells. Surface expression levels of FcεRI in TFE3(-/-) peritoneal mast cells was significantly lower than in control cells. Cultured mast cells derived from TFE3(-/-) mice showed a marked decrease in degranulation and mediator secretion. In vivo experiments showed that the level of plasma histamine in TFE3(-/-) mice after an allergic trigger was substantially less than that seen in WT mice. TFE3 is a novel regulator of mast cell functions and as such could emerge as a new target for the manipulation of allergic diseases.

Evaluation of Mast Cells in Myeloproliferative Disorders and Myelodysplastic Syndromes

Mast cells may be increased as a reactive mastocytosis in various hematologic disorders and malignant neoplasms, as well as in systemic mast cell disease (SMCD). There are no statistical differences in mast cell numbers in reactive mastocytosis and SMCD; however, SMCD usually reveals dyspoietic mast cells and other dyspoietic bone marrow elements. In addition, SMCD is frequently (45%) associated with myeloproliferative disorders (MPDs) (17%) and myelodysplastic syndromes (MDSs) (28%). Thus, it has been suggested that SMCD may represent one aspect of a hematologic disorder that involves multiple bone marrow lineages. To perform a systematic evaluation of MPDs and MDSs without SMCD for dyspoietic mast cells. A total of 55 MPDs or MDSs were reviewed, including 20 cytogenetically proven chronic myeloid leukemias, 6 essential thrombocythemias, 2 polycythemia veras, 21 cytogenetically proven MDSs, and 6 chronic myelomonocytic leukemias. Cases of idiopathic myelofibrosis were not included due to lack of spicules. The bone marrow aspirates were reviewed for an increase in mast cells (1+ to 3+), dyspoietic features within mast cells (decreased cytoplasmic granularity, uneven granule distribution), and a predominance of fusiform mast cells. All cases, except 2 MDSs, had evaluable bone marrow spicules. Of interest, the MPDs were significantly more associated with increased and dyspoietic mast cells (57% and 61%, respectively) than were the MDSs (11% and 4%, respectively). The 2 polycythemia veras and 6 chronic myelomonocytic leukemias did not reveal increased or dyspoietic mast cells. These findings indicate that MPDs (chronic myeloid leukemia and essential thrombocythemia) frequently contain neoplastic mast cells as the spectrum of abnormal bone marrow cells. This feature, in conjunction with other parameters, may possibly be useful in the differential diagnosis of MPDs and MDSs. Our findings, compared with the previously reported findings in SMCD, suggest that SMCD may be more closely related to MPDs than to MDSs.

Mast cell number and phenotype in chronic idiopathic urticaria

Background: Increased levels of histamine have been previously demonstrated in patients with chronic idiopathic urticaria. Objective: The purpose of the study was to determine whether increased numbers of mast cells are present in lesional skin from such patients. Methods: Mast cells have been quantified in lesional ( n = 11) and nonlesional ( n = 9) skin from patients with chronic idiopathic urticaria and compared with site-matched skin from healthy control subjects ( n = 10). Mast cells were identified by using a sensitive, double-labeling immunohistochemical technique with specific monoclonal antibodies to mast cell tryptase and chymase and quantified under light microscopy. Results: No significant differences in mast cell numbers from lesional, nonlesional, or control skin were observed ( p > 0.1, Student's t test). In both patients with urticaria and control subjects, more than 99% of cutaneous mast cells contained tryptase and chymase. Conclusions: These data indicate that increased skin histamine in chronic idiopathic urticaria is not caused by increased mast cells and may alternatively reflect an increase in histamine content per mast cell, enhanced mast cell activation, or recruitment of basophils into skin in patients with chronic idiopathic urticaria. (J A LLERGY C LIN I MMUNOL 1995;96:360-4.)

Mast cells in colorectal neoplasias and premalignant disorders.

Mast cells have recently been found to be well correlated with the prognosis of patients with rectal cancer. This work aimed to characterize the role of mast cells in colonic premalignant conditions. Mast cells were quantified in various colonic disorders, particularly those with premalignant potential. Possible avenues of mast cell action were investigated using these tissue samples, by measuring basement membrane and collagen layer thickening. The mean number of mast cells in carcinoma sections was 0.967/0.9 mm2, in various colorectal neoplasias and related conditions it ranged from 1.36-3/0.9 mm2, and in normal histologic specimens it was 11.90/0.9 mm2. These data established statistically significant differences in mast cell numbers in the colonic disorders studied. The number of mast cells is greatest in the lamina propria level of the colon, a site often not examined because of the limited depth of samples obtained from endoscopic biopsies. Mast cell numbers were found to be correlated to the development from premalignancy to colonic malignancy. Mast cells may be useful as markers of colorectal neoplasia.

Mast cells in female mouse lymph nodes

This study was designed to examine the possible role of sex steroid hormones on mast cells localized in uterus draining lymph nodes (UDLN) in mice. Young virgin estrous animals had more mast cells than diestrous animals in both the UDLN and popliteal lymph nodes (PLN). In retired breeders there were no differences in mast cell numbers of estrous and diestrous animals. There were no differences in mast cell numbers among weanling and older animals in diestrous in the UDLN but, in the PLN, mature animals in either diestrous or estrous had more mast cells than the PLN of weanlings. In mature animals, ovariectomy did not alter mast cell number in either node. However, ovariectomy of weanlings increased mast cell numbers in the PLN but not in the UDLN. These results suggest that the UDLN behaves as a nonclassical target organ for the endocrine system, with mast cell number variations related to gonadal steroid levels.

Mast Cell Participation During the Elicitation of Murine Allergic Contact Hypersensitivity

In order to evaluate mast cell participation in allergic contact hypersensitivity (ACH), BALB/c mice were sensitized with 0.1% trinitrochlorobenzene (TNCB). Immediately before challenge and at 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after challenge with 1% TNCB, groups of animals had ear thickness measured, had blood collected for histamine determinations, and had both ears removed for histologic evaluation of mast cells. The increase in ear swelling was triphasic with peak increases at 1.5 h (14.3 +/- 1.6 X 10(-2) mm; mean +/- SEM), 8 h (19.9 +/- 1.8 X 10(-2) mm), and 24 h (30.2 +/- 2.9 X 10(-2) mm). A triphasic pattern of increased serum histamine was noted at 1-4 h (117% over control levels), at 12 h (131%), and at 48 h (133%). Examination of the tissue specimens from challenged animals showed modest (1+) degranulation of mast cells between 1 and 6 h with extensive (2+) degranulation at 12 h. In addition, hypogranulated mast cells were evident between 1 and 6 h, at 24 h, and at 48 h. There were no statistically significant differences in mast cell numbers at any time. Neither platelets nor other formed elements of the blood contributed to the increased blood histamine levels. These data show that mast cells are activated in a triphasic pattern during ACH, and thus suggest both early and late roles for the mast cell and its products in the evolution of ACH.