Mast cells in human allografted kidney: correlation with interstitial fibrosis.

Mast cells were counted in 78 histologic specimens from 70 patients with various vascular malformations showing cellularly dynamic and cellularly adynamic lesions. In growing stages of strawberry hemangiomas, there was an increased number of mast cells (mean 11.0 cells per high-power field in stage III and 23.7 in stage IV), as well as a high number of mast cells in the initial involution of strawberry hemangiomas (stage V, mean 21.0 cells per high-power field). In later involuting stages (stages VI and VII), the number of mast cells decreased (mean 9.3 in stage VI; mean 4.7 in stage VII). In cellularly adynamic lesions, i.e., port wine stains, the mean number of mast cells was 4.8, and in congenital arteriovenous malformations, it was 3.6. In normal skin, the mean number of mast cells was 3.2. In cellular hemangiomas that showed active growth (stages III to IV), the number of mast cells was strikingly low (mean 1.3). It seems that the mast cells are not responsible for the proliferation of the endothelium or for growth of the hemangioma. The markedly increased number of mast cells in the growing stages and initial involuting stage of strawberry hemangiomas parallels the gradual growth of fibrous connective tissue inside the tumor. Mast cells may thus be a precursor of the beginning of the involution of a strawberry hemangioma.

AB0041 Number of Mast Cell Are Higher in End Stage Knee Osteoarthritis

We estimated the number of mast cells in monkey lungs by both quantitative histologic examination and measurement of total lung histamine, and showed that monkey lungs contain between 10(7) and 10(8) mast cells, with approximately 83% of these being located in conducting airways, and 17% in the parenchyma. The number of mast cells found in each airway generation increased from approximately 60,000 in the trachea to 8 million in the terminal bronchioles. In airways from different generations the number of mast cells superficial to the basement membrane in the epithelium and lumen (EMC) was compared to the number of mast cells found in the submucosa between basement membrane and cartilage and to the number of those found outside the cartilage. The number of EMC varied between animals and ranged from 0-0.4% of the total number of mast cells in the trachea, to 0-27% of the total in the terminal bronchioles. On the average, EMC accounted for 12% of the total number of mast cells in conducting airways, where we calculate that there is approximately one EMC for every 100,000 epithelial cells. Eosinophils were distributed in close relation to mast cells in the mucosa and submucosa, but were rare outside the cartilage. We conclude that the number of mast cells increases from central to peripheral airways and that this may account for the marked peripheral airway response observed after antigen challenge.

Tryptase-containing mast cells have recently been found to be increased in the upper dermis of psoriatic lesions. In the present study, the distribution of chymase- and tryptase-containing mast cells was morphometrically analysed at different dermal levels of lesional and non-lesional psoriatic skin (12 patients) as well as normal human skin. Mast cell tryptase was identified enzyme-histochemically, using Z-Gly-Pro-Arg-MNA as the substrate. For demonstrating mast cell chymase, a simple and specific enzyme-histochemical staining method was developed, using Suc-Val-Pro-Phe-MNA as the substrate. All mast cells positive for chymase were also positive for tryptase and Giemsa stain. Although the number of tryptase-positive mast cells was slightly increased throughout the dermis of lesional psoriatic skin, this increase was most pronounced in the upper dermis immediately beneath, and in close contact with, the epidermis. In contrast, the number of chymase-positive mast cells was clearly decreased in the upper dermis of psoriatic lesions, but not in the deeper dermis, as compared with non-lesional psoriatic skin. In addition, all chymase-positive mast cells observed in the upper dermis were very weakly stained when compared with those in the deeper dermis. No differences were found between non-lesional psoriatic skin and normal skin in which the number of mast cells containing chymase was 72-73% of the number containing tryptase. The present results suggest that T mast cells particularly, containing tryptase but no chymase, proliferate in psoriatic lesions, and that the increase in tryptase activity and the decrease in chymase activity in the upper dermis may lead to an imbalance in the biochemical regulatory systems.

Contribution of mast cells to the tubulointerstitial lesions in IgA nephritis

During the pandemic of the new coronavirus infection COVID-19 the question about the importance of mast cells and their proteases arose. The aim of this study is to determine the role of mast cells and their proteases chymase and tryptase in the pathogenesis of severe COVID-19. Materials and methods. The study included 55 patients: 29 male (52,7 %) and 26 female (47,3 %) aged 67 [62;71] years with severe COVID-19 and fatal outcome. An analysis of postmortem lung biopsies of patients with COVID-19 was carried out, determining the representation of mast cells, protease profile and degranulation activity. A correlation analysis was carried out between mast cell and clinical and laboratory parameters of patients. Results. Increased number of mast cells and their degranulation activity were found in patients with chronic heart failure, obesity, chronic kidney disease, coronary heart disease and acute cerebrovascular accident. Degranulation of tryptase-positive mast cells are depleted as the duration of the disease increases: the content of single tryptase-positive mast cells (%) negatively correlates with the duration of the disease and hospitalization (p = 0,015, r = -0,327 and p = 0,006, r = -0,368, respectively), the content of tryptase-positive mast cells fragments (%)correlates with the duration of hospitalization (p = 0,007, r = 0,357). Correlations were established between the levels of non-conjugated bilirubin and alanine aminotransferase with the content of single tryptase-positive mast cells (per mm2) (r = 0,340, p < 0,05 and r = 0,307, p < 0,05, respectively), as well as single degranulated tryptase-positive mast cells (per mm2) (r = 0,369, p < 0,05 and r = 0,363, p < 0,01, respectively), and the level of conjugated bilirubin with the content of single tryptase-positive mast cells (%) (r = 0,415, p < 0,05). The blood calcium level correlates with the absolute total content of single tryptase-positive mast cells (p = 0,013, r = 0,457), as well as degranulated (p = 0,017, r = 0,441). A negative correlation was also found between potassium level and the relative content of single non-degranulated tryptase-positive mast cells (p = 0,014, r = -0,352). Correlations were found between the level of total bilirubin at the time of admission and over time with the content of single degranulated chymase-positive mast cells (per mm2) (p = 0,043, r = 0,277 and p = 0,027, r = 0,317, respectively). Urea level upon admission positively correlates with the absolute total content of single chymase-positive mast cells (p = 0,045, r = 0,277), as well as degranulated (p = 0,04, r = 0,283). The potassium level in the blood correlates with the total content of co-adjacent chymase-positive mast cells (p < 0,05, r = 0,388), as well as content of co-adjacent degranulated chymase-positive mast cells (p < 0,05, r = 0,388). Conclusion. Significant correlations were noted between mast cells parameters and duration of the disease and hospitalization, the presence of comorbidities, unconjugated and conjugated bilirubin, ALT, urea, total protein, sodium, potassium and calcium blood levels. An increase in the number of mast cells and their degranulation activity has been found in patients with comorbidities: chronic heart failure, obesity, chronic kidney disease, ischemic heart disease and previous stroke. The revealed depletion of degranulation processes of tryptase-positive mast cells as the duration of the disease increases indicates their role in lung damage. We noted participation of mast cells and their proteases chymase and tryptase in the development of liver and kidney damage in patients with COVID-19, which confirms their importance in the severe course of the disease and may be considered in the future for the development of pathogenetic therapy.

This study was performed in order to assess whether acute stress can increase mast cell and enterochromaffin (EC) cell numbers, and proteinase-activated receptor-2 (PAR2) expression in the rat colon. In addition, we aimed to investigate the involvement of corticotrophin-releasing factor in these stress-related alterations. Eighteen adult rats were divided into 3 experimental groups: 1) a saline-pretreated non-stressed group, 2) a saline-pretreated stressed group, and 3) an astressin-pretreated stressed group. The numbers of mast cells, EC cells, and PAR2-positive cells were counted in 6 high power fields. In proximal colonic segments, mast cell numbers of stressed rats tended to be higher than those of non-stressed rats, and their PAR2-positive cell numbers were significantly higher than those of non-stressed rats. In distal colonic segments, mast cell numbers and PAR2-positive cell numbers of stressed rats were significantly higher than those of non-stressed rats. Mast cell and PAR2-positive cell numbers of astressin-pretreated stressed rats were significantly lower than those of saline-pretreated stressed rats. EC cell numbers did not differ among the three experimental groups. Acute stress in rats increases mast cell numbers and mucosal PAR2 expression in the colon. These stress-related alterations seem to be mediated by release of corticotrophin-releasing factor.

Because mast cell proliferation has been reported in disorders of abnormal bone remodeling, we quantitated the number of mast cells in undecalcified section of iliac crest bone from 16 untreated women with postmenopausal osteoporosis and contrasted the findings to values from 10 normal women and 12 normal men. The mean number of marrow mast cells was greater in normal women than men (1.17 vs 0.40 cells per mm2, P less than 0.05). Compared to the normal women, osteoporotic women had a greater number of mast cells in the marrow (3.38 vs 1.17 cells per mm2, P less than 0.01). However, there was no statistically significant correlation between the number of marrow mast cells and either the patient's age or the severity of the bone lesions, as assessed by histomorphometry. Our findings confirm the association between increased numbers of mast cells and postmenopausal osteoporosis.

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.

An association was found in rats of different strains between the susceptibility to EAU and the number of mast cells in the choroid of the eye. High responder rats (Lewis, CAR) had strikingly more choroidal mast cells than the low responder BN animals, whereas intermediate numbers of mast cells were found in the F1 hybrids of Lewis and BN (LBNF), which exhibited an average level of susceptibility to EAU. LeR rats, derived from the Lewis strain, developed EAU only when treated with B. pertussis, and their number of choroidal mast cells was only about 1/5 of that found in the Lewis rats. Unlike the differences in the number of choroidal mast cells, small variations were found in the skin mast cell numbers of the tested rats. It is proposed that the number of local mast cells may be one mechanism by which the susceptibility to an organ-specific autoimmune disease is genetically regulated.

Brain mast cell numbers in the albino rat: sources of variability

Data obtained from animal and human studies support the existence of mast cells (MC) in the gastrointestinal (GI) tract, where they are considered important for the control of luminal parasites and possibly other microorganisms. MC are also implicated in food allergies, GI inflammation, and functional GI diseases, including irritable bowel syndrome (IBS) [1]. MC density may be increased in inflammatory bowel disease (IBD) and IBS, although such studies have yielded variable and sometimes contradictory results, likely due to methodological problems such as sampling issues, poorly characterized MC identification methodology, and lack of adequate documentation of disease correlates. There is no question that MC numbers are likely to be easier to identify and count in lesional areas as they may be present in IBD. MC density in the terminal ileum had previously been reported to be significantly increased in patients with IBS, even though MC abundance only correlated weakly with IBS symptoms, and, in some cases, a decreased density of colonic c-kit-positive in IgEor IgG-stained MC, was reported [2], even though IgEor IgG-staining is not an index of MC activation. In the paper by Choi et al. [3] published in this issue of Digestive Diseases and Sciences, the authors analyzed intestinal MC density in: (a) diverse patient cohorts, including diarrhea predominant-IBS (D-IBS), ulcerative colitis (UC) in remission, mild UC, and in healthy controls; (b) random colonic biopsies; (c) different colonic segments; and (d) mucosal MC and lamina propria/intra-epithelial T lymphocytes. The results are important because MC number was significantly increased in 97.6 % of D-IBS patients, intra-epithelial lymphocytes (IEL) were increased in 92.8 %, and lamina propria lymphocytes (LPL) were increased in 81.9 %. Moreover, even though the numbers of immune cells were even higher in some post-infectious (PI)-IBS patients, the remaining D-IBS patients had a significantly higher number of these cells compared with controls. Immunochemically identified were tryptase-positive MC and CD3-positive T cells (and not for all lymphocytes, as the authors stated). All publications to date, including the one by Choi et al. [3], did not report MC activation, which, according to some, is more important than actual numbers [4]. For instance, tryptase staining underestimates the number of degranulated MC, since released secretory granule tryptase does not stain. One way to identify degranulated MC is to stain for c-kit (CD117), the surface MC receptor for stem cell factor. Nevertheless, since mediator secretion can also occur without degranulation [5], MC activation can best be identified either by ultrastructural appearance T. C. Theoharides (&) Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA e-mail: theoharis.theoharides@tufts.edu

Cardiac mast cells in the transition to heart failure

BackgroundThe D-mannose binding lectin ArtinM is known to recruit neutrophils, to degranulate mast cells and may have potential therapeutic applications. However, the effect of ArtinM on mast cell recruitment has not been investigated.MethodologyMale Wistar rats were injected i.p. with ArtinM or ConA (control). The ability of the lectin to degranulate peritoneal and mesenteric mast cells was examined. Recruitment of mast cells to the peritoneal cavity and mesentery after ArtinM injection was examined with or without depletion of peritoneal mast cells by distilled water.ResultsArtinM degranulated both peritoneal and mesentery mast cells in vitro. Three days after i.p. injection of the lectin there were reduced numbers of mast cells in the peritoneal lavage, while at 7 days post injection of ArtinM, the number of peritoneal mast cells was close to control values. Since immature mast cells are recruited from the bone marrow, the effect of the lectin on bone marrow mast cells was examined. Injection of ArtinM resulted in an increased number of mast cells in the bone marrow. To determine if degranulation of mast cells in the peritoneal cavity was required for the increase in bone marrow mast cells, the peritoneal cavity was depleted of mast cells with ultrapure water. Exposure to ArtinM increased the number of mast cells in the bone marrow of rats depleted of peritoneal mast cells.ConclusionsThe ArtinM induced recruitment of mast cells from the bone marrow to the peritoneal cavity may partially explain the therapeutic actions of ArtinM.

The distribution of mast cells in various ovarian compartments was studied during different stages of the reproductive cycles in Rattus rattus. Two types of mast cell populations were recognized with light microscopy i.e., light purple and deep purple, the latter also includes deeply stained cells with extruded granules. Mast cells identified by electron microscopy showed the ultrastructural features during granule formation and release of their content. Significantly higher numbers of mast cells per unit area of ovary were seen at estrus and diestrus. Numbers of mast cells also remained high during pregnancy with possible involvement of mast cell products in vascularization of corpora lutea. A positive correlation existed between mast cell counts and embryo number during pregnancy. However, numbers of mast cells declined significantly after parturition.