Granulocytes are a category of white blood cells that are a component of the body’s innate immune system. They are characterized by granules in their cytoplasm and a nucleus with a multi-lobed shape. The three types of granulocytes are neutrophils, eosinophils, and basophils. Each type has a specialized role in defending the body against pathogens, and their collective function is to identify and eliminate foreign invaders through inflammatory reactions.
The Origin in Hematopoiesis
All granulocytes originate from a hematopoietic stem cell (HSC) in the bone marrow. This process, known as hematopoiesis, begins when an HSC commits to one of two paths: a common lymphoid progenitor for lymphocytes, or a common myeloid progenitor (CMP). The CMP is the starting point for all myeloid cells, including granulocytes.
Influenced by specific signaling molecules, the CMP develops into a granulocyte-monocyte progenitor (GMP). This progenitor cell is the direct precursor to the granulocyte lineage, setting it on a path away from other myeloid cells like red blood cells and platelets.
Stages of Granulocyte Maturation
The maturation of granulocytes from progenitor cells is a process called granulopoiesis, which begins with the myeloblast. This is the first recognizable cell in the lineage, characterized by a large, oval nucleus and minimal cytoplasm. At this early stage, the cell is actively dividing but lacks its defining granules.
The cell then transforms into a promyelocyte, which is often larger and distinguished by the appearance of primary (azurophilic) granules containing enzymes like myeloperoxidase. The nucleus remains large and round, but the cytoplasm is more abundant.
In the myelocyte stage, the cell and its nucleus shrink. A defining feature is the synthesis of secondary (specific) granules, whose contents determine if the cell becomes a neutrophil, eosinophil, or basophil. Cell division continues through this stage.
The cell then enters the metamyelocyte stage, where cell division ceases. The nucleus becomes indented into a kidney-like shape, and the cell continues to accumulate granules. This stage marks the beginning of the post-mitotic phase of maturation.
The nucleus continues to change shape as the cell becomes a band cell, where it elongates into a “U” shape. The cytoplasm is filled with mature granules, and the cell is considered an immature granulocyte. The presence of band cells in the bloodstream can indicate an active infection.
The Three Mature Granulocytes
Neutrophils are the most abundant granulocyte, making up 50-70% of circulating white blood cells. They are recognized by a multi-lobed nucleus with two to five lobes connected by thin strands. As first responders to bacterial and fungal infections, neutrophils are phagocytic, meaning they engulf and digest invading microorganisms using enzymes from their granules.
Eosinophils constitute 1-3% of circulating white blood cells and are characterized by a bi-lobed nucleus. Their large cytoplasmic granules stain a distinct pink or red with the acidic dye eosin. The primary function of eosinophils is to combat parasitic infections, like helminth worms, by releasing toxic proteins from their granules. They are also involved in modulating allergic inflammatory responses.
Basophils are the rarest granulocyte, comprising less than 1% of white blood cells. Their most prominent feature is large, dark blue or purple-staining granules that often obscure their bi-lobed nucleus. Basophils are central to allergic reactions, releasing histamine and other chemical mediators from their granules to promote blood flow and initiate an inflammatory response.
Regulation of Granulopoiesis
The production of granulocytes (granulopoiesis) is a regulated process the body adjusts based on needs like infection. This regulation is orchestrated by signaling molecules called cytokines and growth factors, which instruct the bone marrow to alter the production and maturation of blood cells.
Two main regulators are Granulocyte Colony-Stimulating Factor (G-CSF) and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF). G-CSF specifically encourages the development of cells in the neutrophil lineage. GM-CSF has a broader effect, stimulating the production of both neutrophils and macrophages. These factors signal the bone marrow to accelerate granulopoiesis to meet immune demand.
During an infection, other immune and endothelial cells release these growth factors, creating a positive feedback loop. This surge in G-CSF and GM-CSF ensures a rapid deployment of granulocytes to the site of infection to bolster the body’s defenses.
Clinical Significance of Granulocyte Development
Proper granulocyte development is linked to human health, as disruptions in this process can lead to medical conditions. An abnormally low number of neutrophils, a condition known as neutropenia, compromises the body’s ability to fight bacterial infections, leaving an individual highly susceptible to illness.
Conversely, an abnormally high number of neutrophils is called neutrophilia. While often a normal response to infection, persistent neutrophilia can indicate a more serious issue. Uncontrolled proliferation of granulocyte precursors is a hallmark of blood cancers like Chronic Myeloid Leukemia (CML) and Chronic Neutrophilic Leukemia (CNL). In these diseases, the bone marrow produces an excessive number of granulocytes that can crowd out other necessary blood cells.