Mast cell degranulation is a rapid, protective mechanism of the immune system that can also become the source of allergic reactions. This process involves specialized immune cells, called mast cells, quickly releasing a potent cocktail of chemical messengers into the surrounding tissue. The sudden discharge of these substances is a programmed response to neutralize threats like pathogens or toxins. However, it is best known for its role in the immediate hypersensitivity response, commonly referred to as an allergy. Understanding this cellular event is fundamental to grasping how the body initiates a fast, localized defense and how that same system can sometimes overreact to harmless substances.
Understanding Mast Cells
Mast cells are a type of immune cell derived from hematopoietic stem cells in the bone marrow. Unlike most white blood cells, they circulate as immature progenitor cells and only fully mature once they have settled into various tissues throughout the body. They are strategically positioned in connective tissues that act as interfaces with the external environment, such as the skin, the lining of the lungs, and the gastrointestinal tract.
These cells are also frequently found near blood vessels and nerves. A defining physical feature of a mature mast cell is its cytoplasm, which is densely packed with numerous large, internal storage vesicles called granules. These granules contain a variety of pre-formed chemical substances, poised for instantaneous release upon cell activation.
The Triggering of Degranulation
The most recognized way for a mast cell to initiate degranulation is through an immunological trigger involving Immunoglobulin E (IgE) antibodies. The mast cell surface is decorated with high-affinity IgE receptors, which are already bound to circulating IgE molecules. When an allergen, such as pollen or a food protein, enters the body, it can cross-link two or more of these IgE molecules attached to the receptors.
This cross-linking event instantly activates the mast cell. The binding initiates a rapid cascade of intracellular signaling, including the activation of tyrosine kinases, which instructs the cell to release its contents. This signaling leads to the fusion of the internal granules with the outer plasma membrane of the cell.
While IgE-mediated activation is the classic pathway, mast cells can also be triggered by non-immunological stimuli. Certain drugs, neuropeptides released from surrounding nerves, and components of the complement system can directly activate the mast cell through different surface receptors. This non-IgE activation pathway allows the mast cell to respond to a broader range of threats, including physical injury and bacterial components.
Key Chemical Mediators Released
The substances released during degranulation are categorized into pre-formed mediators and newly synthesized mediators. Pre-formed mediators are stored in the granules and are released within seconds to minutes of activation. The most well-known of these is histamine, which is responsible for causing immediate effects like vasodilation and increased vascular permeability.
Other pre-formed components include tryptase and chymase, which are proteases that help break down surrounding tissue to allow immune cells to move into the area. Newly synthesized mediators are not stored, but are rapidly created and released by the mast cell minutes after activation. This group includes lipid-based signaling molecules like prostaglandins and leukotrienes.
Leukotrienes are potent stimulants for bronchoconstriction and mucus production in the airways. The mast cell also synthesizes and releases various cytokines, which are proteins that help coordinate and prolong the inflammatory response by recruiting other immune cells to the site. The combined effect of these mediators dictates the nature and severity of the ensuing biological reaction.
Physiological Impact on the Body
The sudden flood of chemical mediators from degranulation causes physiological effects that are the hallmarks of Type I immediate hypersensitivity reactions. Histamine’s action on blood vessels leads to localized redness and swelling, as the vessels expand and become leaky, allowing fluid to pool in the tissue. This rapid increase in vascular permeability is a protective measure designed to deliver immune components to the site of invasion.
In the respiratory tract, the release of leukotrienes and histamine results in the contraction of smooth muscle, leading to symptoms like wheezing, coughing, and difficulty breathing, as seen in asthma. When degranulation occurs throughout the body, the systemic release of mediators can cause anaphylaxis, a rapid, life-threatening reaction. Widespread vasodilation causes a sudden drop in blood pressure, while simultaneous bronchoconstriction severely impairs breathing, requiring immediate medical intervention.