Emerging Mast Cell Research and Methods

Ever wondered how a simple sniffle could turn into a full-blown allergic reaction?

The answer lies within tiny but mighty mast cells. Food allergies have risen dramatically in recent years, with approximately 33 million people reporting at least one food allergy in the United States alone.1 Mast cells are strategically positioned throughout the body, particularly in tissues that interface with the external environment, such as the skin, digestive tract, nose, and lungs. When activated, these cells release granules containing histamine, proteases, heparin, and cytokines, triggering allergic responses that can manifest as diarrhea, hives, or even life-threatening anaphylaxis. Now, more than ever, researchers seek to understand the mechanisms regulating mast cell activation, proliferation, and degranulation to address this growing health concern.

Clinton Mathias Ph.D., an associate professor and researcher from the University of Connecticut (UConn), and his colleague, Sallie Schneider Ph.D., a leading expert in histology at HistoSpring, are working in tandem to further mast cell research. Together, they have co-authored numerous research studies to better understand the mast cell’s unique role in various health conditions such as food allergy and allergic airway disease. By studying the development, heterogeneity, activation mechanisms, and involvement in allergic and autoimmune diseases, Mathias, Schneider, and co-researchers aim to identify new targets for treating allergic and immune conditions.

Mast Cell Research Discoveries
Current research demonstrates the role of cytokines and epigenetic changes in food allergies and the influence of epigenetic modifications on mast cell function. Epigenetics refers to gene expression changes that do not involve alterations in the DNA sequence itself. One particular study investigates how dietary factors and medications can impact these epigenetic modifications, leading to either suppression or enhancement of mast cell activity in food allergies.2 This research highlights the potential for targeting epigenetic mechanisms to modulate mast cell function and develop new therapeutic approaches for food allergies.

A separate paper examines food allergies further by examining the specific role of the cytokine IL-10 in mast cell function.  Traditionally viewed as an anti-inflammatory cytokine, IL-10 is surprisingly shown to promote mast cell expansion and activation in this context. This unexpected finding suggests that IL-10 may contribute to the development and severity of food allergies.3

Further research again challenged IL-10 as an anti-inflammatory cytokine. Mathias’s 2024 publication in The Journal of Immunology reveals that
IL-10 can amplify mast cell activation and degranulation in response to IL-33, a potent inflammatory cytokine. This unexpected finding suggests that IL-10 can suppress and exacerbate inflammation, depending on context. These findings show the complex role of IL-10 in regulating immune responses and suggest that targeting IL-10 signaling pathways may have therapeutic potential for treating allergic diseases and other inflammatory conditions.4 In this recent research, a specialty stain called chloroacetate esterase was used to detect changes in the accumulation of mast cells in the digestive tract of rodents triggered to undergo an allergic response.

Understanding the complex world of immune cells often requires specialized techniques such as the abovementioned chloroacetate esterase stain. HistoSpring’s specialized histochemical techniques support researchers through a powerful arsenal of specialty mast cell stains for visualizing and analyzing these cells. Mast cell stains can:

  • Identify and quantify mast cells in tissues
  • Assess the activation state of mast cells 
  • Localize mast cells in specific tissues
  • Help monitor the response of mast cells to various stimuli

In addition to these functions, the following are some specific stain types offered by HistoSpring that provide unique advantages when studying these multifaceted immune cells:

Naphthol-AS-D-chloroacetate Esterase
Naphthol AS-D chloroacetate esterase highlights key immune system cells called granulocytes by targeting the chloroacetate esterase (ChAE) enzyme. This stain enables clear visualization of these cells in various biological samples, including blood smears, bone marrow, and tissue sections. Its mechanism involves the activation of ChAE by the substrate Naphthol AS-D chloroacetate, which, upon enzymatic breakdown, reacts with a diazonium compound to produce a visible color deposit. This staining technique is widely applicable, allowing for the assessment of granulocyte differentiation and distribution in diverse biological contexts.5 While primarily specific for granulocytes, it’s essential to recognize that certain other cell types, such as mast cells, may exhibit some positive staining.

Toluidine Blue
Toluidine blue, a workhorse stain in histology, plays a strong role in identifying mast cells. This metachromatic dye paints mast cell granules a distinctive red-violet. The staining intensity is influenced by the pH of the solution, with lower pH levels better suited for revealing benign mast cell lesions. Beyond its diagnostic prowess in mast cell tumors, toluidine blue can be used for a wider range of applications, such as pinpointing oral premalignant lesions and guiding surgeons during their removal. Even cancer diagnosis benefits from toluidine blue, as it helps show cervical mucosal abnormalities, vulvar cancer, and precancerous and cancerous lesions in the oral cavity and throat. Its utility also extends to lung cancer detection by staining imprint smears taken during bronchoscopies.6

Mast Cell Staining Services
By leveraging HistoSpring’s advanced histology and mast cell staining capabilities, researchers can gain valuable insights into the presence and behavior of mast cells within tissues. This detailed information is crucial for deciphering the role of mast cells in various health conditions and developing targeted therapies to benefit the growing population. 

References

  1. Food Allergy Research & Education. Facts and statistics. Food Allergy Research & Education. Published 2022. https://www.foodallergy.org/resources/facts-and-statistics
  2. Krajewski D, Kaczenski E, Rovatti J, et al. Epigenetic Regulation via Altered Histone Acetylation Results in Suppression of Mast Cell Function and Mast Cell-Mediated Food Allergic Responses. Frontiers in Immunology. 2018;9. doi:https://doi.org/10.3389/fimmu.2018.02414
  3. Polukort S, Rovatti J, Carlson L, et al. IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10–Deficient Mice. Journal of Immunology. 2016;196(12):4865-4876. doi:https://doi.org/10.4049/jimmunol.1600066
  4. Saurav Ranjitkar, Krajewski D, Garcia C, et al. IL-10 Differentially Promotes Mast Cell Responsiveness to IL-33, Resulting in Enhancement of Type 2 Inflammation and Suppression of Neutrophilia. The journal of immunology/The Journal of immunology. Published online March 18, 2024. doi:https://doi.org/10.4049/jimmunol.2300884
  5. Dmitri Atiakshin, Kostin A, Igor Buchwalow, Morozow D, Samoilova V, Tiemann M. Chloroacetate esterase reaction combined with immunohistochemical characterization of the specific tissue microenvironment of mast cells. Histochemistry and cell biology. 2023;159(4):353-361. doi:https://doi.org/10.1007/s00418-022-02174-1
  6. Chowdhury A, Bhattacharya R, Panda J, Chakrabarty D. Toluidine Blue Stain as a Rapid Onsite Tool for Preliminary Diagnosis in Imprint Smears of Bronchoscopic Biopsy: A Cytohistopathological Correlation. Journal of laboratory physicians. 2023;15(04):562-566. doi:https://doi.org/10.1055/s-0043-1768953

#Allergy research #histology #Immunochemistry #IHC #tissue microenvironment #food allergy