Eosinophils vs. Basophils vs. Neutrophils

Eosinophils, basophils and neutrophils are granulocytes found in the blood. Granulocytes, the most common type of white blood cells, have small granules that release enzymes when your immune system is under attack. This occurs during an infection, allergic reaction or asthma episode. Granulocytes are produced from stem cells in the bone marrow and live only for a few days.

Granulocytes work together to rid your body of infection or allergens. Each type of granulocyte has its own combination of chemicals and enzymes in its granules. As a result, each type has different functions:

Eosinophils - These granulocytes are present in almost all immune responses, most notably allergies. However, they are also resistant to parasites.

Basophils - These granulocytes primarily combat allergic reactions. They release histamine and the blood thinner heparin.

Neutrophils - The most common type of granulocyte, neutrophils attack bacteria. Each neutrophil can consume up to 20 bacteria during its lifetime.

What are Eosinophils?

Eosinophils are granulocytes with a bilobed nucleus characterized by highly condensed chromatin. They possess acidophilic granules with electron-dense cores upon ultrastructural examination. Only 1-5% of circulating leukocytes are eosinophils.

Eosinophils are involved in the triggering of inflammatory responses in allergic disorders. They also combat multicellular parasites like helminth. In response to chemokine and cytokine signals, eosinophils migrate into inflammatory tissues. Eosinophils, along with basophils and mast cells, mediate allergic reaction and asthma pathogenesis. Eosinophils present antigens of the destroyed cells to T helper cells. Through the activation of eosinophils, cytokines like TNF alpha and interleukins, growth factors like TGF beta and VEGF are produced.

Eosinophil Markers

Common granule proteins found in eosinophils include major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN). Eosinophils release these granule proteins extracellularly to combat parasites, which are too large to be phagocytosed by neutrophils. These granulocytes also possess liposomes, which are formed upon eosinophil activation and are involved in eicosanoid synthesis.

Classically, eosinophils have been defined as CD45+CD11b+CD11c+CD13+CD15+CD33+. Eosinophils have been reported to express the following series of markers: immunoglobulin receptors (FCGR2A), complement receptors (CR1, CR3), cytokine receptor (IL3RA, IL2RA), adhesion molecules (ITGA4), prostaglandin receptors (PTGDR2), platelet-activating factor receptor (PTAFR), and sialic acid-binding Ig-like lectin 8 (SIGLEC8).

Like neutrophils, eosinophils express IL5RA, CCR3, TLR7, TLR8, ITGAM, ITGAX, ANPEP, CD33, CEACAM8, FUT4, and CD65. Of note, although IL5RA can be expressed by neutrophils, its expression is more commonly associated with eosinophils, which rely on the receptor for maturation and survival via the cytokine IL-5. Indeed, IL-5 has been shown to confer eosinophilic properties in neutrophils, revealing a potential capacity for trans-differentiation among granulocytes. Similarly, CCR3 and CCR5 are more typical for eosinophils but have also been reported on neutrophils; and, more perplexingly, neutrophils have been shown to produce the eosinophil granule ECP.

What are Basophils?

Basophils are the rarest of granulocytes, accounting for less than 1% of circulating leukocytes. Despite their lobed nuclei, basophils are functionally and molecularly similar to mast cells, participating also in acute and chronic allergic responses. They contain the anticoagulant, heparin, which prevents the blood from clotting quickly. The enzymes in their granules are released during asthma. Compared to other granulocytes, basophils are the least common in the blood. They are also the largest granulocytes. Basophils also function as phagocytes. They also produce serotonin and histamine, which induce inflammation. Basophils play a role in defending against viral infections. Leukotrienes and some interleukins are secreted by activated basophils.

Basophil Markers

Basophils express FCER1A (FcεR1), cytokine and chemokine receptors (IL3RA, IL5RA, IL2RA, CCR2, CCR3), enzymes (ENPP3), and CD33. Unlike mast cells, basophils differentiate in the bone marrow and seldom proliferate after maturation.

Genes expressed uniquely by basophils (among granulocytes, at least) include CD36, CD38, CD40LG, and CD9.

What are Neutrophils?

Neutrophils are a type of granulocytes with a multi-lobed nucleus of 2 to 5 lobes, with a higher number generally indicating a more mature neutrophil. These cells account for as much as 70% of all circulating leukocytes in an adult and play a key role in innate immunity by phagocytosing microorganisms and degrading them with cytotoxic granule proteins. During phagocytosis, a vesicle, the phagosome, is formed from the plasma membrane and surrounds the bacterium in the extracellular matrix. The vesicles are pinched off into the cytoplasm and transported into lysosomes. Phagolysosomes are formed by the fusion of lysosomes with phagosomes. Digestion of engulfed bacteria occurs inside the phagolysosomes. The waste produced during digestion is excreted through exocytosis. Neutrophils are among the first cells to migrate to the sites of inflammation, following cytokine signals such as IL-8. This process of migration is called chemotaxis.

Neutrophil Markers

Early neutrophil precursors express cytoplasmic myeloperoxidase (MPO), ANPEP (CD13), and CD33. Upon maturation, these cells sequentially upregulate effector molecules, including ITGAM (CD11b), FCGR3A (CD16), and MME (CD10). Neutrophils express ANPEP periodically throughout maturation. Sialylated carbohydrate antigen CD65 is another indicator of maturity, as its presence appears only after the progenitor marker CD34 has disappeared.

Like many immune cells, neutrophils express a broad range of cellular markers that can be used for identification and functional characterization. These include cytokine and chemokine receptors (IL5RA, CCR3, CCR5, CXCR2), pattern recognition receptors (CD14, TLR7, TLR8), adhesion molecules (ITGAM, IGTAX, CEACAM8, CD65), and enzymes (MME, ANPEP, FUT4, MPO). Other commonly expressed neutrophil receptors include CD33 and FCGR3A (CD16). MPO is an important granule protein used by neutrophils to destroy microorganisms.

Table 1. Differences between eosinophils, basophils, and neutrophils.

Eosinophils Basophils Neutrophils
Nucleus Two-lobed nucleus Bean-shaped nucleus Multi-lobed nucleus, can be 2-5
Function Involved in triggering inflammatory responses in allergic disorders Contain anticoagulant heparin, preventing quick blood clotting Engulf bacteria in the extracellular matrix through phagocytosis
Staining color Brick-red Dark blue Natural pink
Diameter 12-17 µm 10-14 µm 8.85 µm
Abundance 1-6% of white blood cells 0.5-1% of white blood cells 40-75% of white blood cells
Lifespan 8-12 hours in circulation, 8-12 days in tissues 60-70 hours 5-90 hours
Granules Histamines, Rnase, Dnase, eosinophil peroxidase, plasminogen, lipase and major basic proteins Histamine, proteolytic enzymes like elastase and lysophospholipase, and proteoglycans like heparin and chondroitin Lysozyme, phopholipase A2, acid hydrolases, myeloperoxidase, elastase, serine proteases, cathepsin G, proteinase 3, proteoglycans, defensins and bacterial permeability increasing protein
Secretions Cytokines like TNF alpha and interleukins, growth factors like TGF beta and VEGF Leukotrienes, some interleukins Activated neutrophils produce neutrophil extracellular traps (NETs).

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