Mast Cells

Summary

Mast cells are white blood cells of the innate immune system that primarily reside in peripheral tissues. They are granulocytes that have basophilic-staining granules on H&E. They are activated in many ways, including: trauma, IgE aggregation, C3a, C5a, and by drugs including vancomycin. Upon activation, mast cells degranulate to release histamine, heparin, eosinophil chemotactic factors like Interleukin-5 (IL-5), and tryptase. Although mast cell degranulation is good in response to injury or infection, aberrant mast cells degranulation results in allergy and anaphylaxis. Abnormal mast cell activation also contributes to the pathophysiology of asthma. The mast cell-stabilizing drugs cromolyn and nedocromil can be used to prevent mast cell degranulation, which can be useful in the treatment of asthma and allergy. 

Key Points

• Mast Cells 
  • White blood cells of the innate immune system
  • Contains basophilic granules (blue) on H&E
    • Similar appearance and functions as basophils, with different hematopoietic origin
  • Activated by:
    • Tissue trauma
    • Anaphylatoxins (C3a and C5a)
      • Produced in Common Complement Activation
    • Binding to Immunoglobulin E (IgE)
      • Fc-epsilon receptors detect IgE aggregation on surface of pathogen
    • Direct activation by drugs (e.g. Vancomycin, opioids, and radiocontrast dye)
      • Red Man syndrome seen with vancomycin use is mediated by IgE-independent mast cell degranulation
  • Degranulation leads to the release of:
    • Histamine
      • Mediates allergic reactions/anaphylaxis
        • Also called Type 1 Hypersensitivity Reactions
      • Pathogenic in urticaria (hives) 
        • Caused by focal lgE-mediated degranulation of mast cells
      • Mediates bronchial/allergic asthma
    • Heparin 
    • Tryptase
      • Used as a marker for mast cell activation, e.g. in drug allergy
    • Eosinophil chemotactic factors (e.g. IL-5)
      • Other inflammatory cytokines, including leukotrienes, prostaglandins, platelet-activating factor, interleukin-4, etc.
  • Inhibit degranulation with cromolyn sodium and nedocromil
    • Mast cell stabilizer drugs used to treat asthma and allergy
  • Levels elevated in systemic mastocytosis
    • Abnormal proliferation of mast cells and increased histamine production
    • Excess histamine may lead to development of gastric ulcers