EosinophilsAnneka Pierzga & Geoffrey Latner | MLT 1042 | April 16, 2016 | College of Southern Maryland

Maturation

Hypersegmentation

What is an Eosinophil?

Eosinophilia

Chediak-Higashi Syndrome

• The Chediak-Higashi syndrome is a rare autosomal recessive condition associated with abnormally large leukocyte granules resulting from fusion of lysozymes. This disorder may affect granulocytes, leukocytes, and monocytes (UVA).

• Phagocytosis is defective. Platelets lack dense granules and platelet function is abnormal (UVA).

Bibliography

• Eosinophilia occurs in association with hypersensitivity reactions, parasitic infestations, cancers (Hodgkin's disease, eosinophilic leukemia). (Blumenreich, 1990, p. 726)

• Blood smear presents high percentage of eosinophils, as shown in the picture above.

• A 100 cell differential count of 5 or more eosinophils is the basis for diagnosing eosinophilia.

Pluripotent Stem Cell Myeloid Stem Cell CFU-GEMM

CFU-Eo Myeloblast

EosinophilicMyelocyte

EosinophilicMetamyelocyte

EosinophilicBand

Eosinophil

Size: 12-18µmNucleus: round to oval; may have 1 flattened sideNucleoli: not visibleChromatin: coarse; more condensed than promyelocytePrimary Granules: few to moderateSecondary Granules: variable number of refractile orange granulesN/C Ratio: 2:1 to 1:1

“Dawn of Eosinophilia”

Size: 10-15µmNucleus: kidney bean shape; indentation < 50% width of nucleusNucleoli: not visibleChromatin: coarse, clumpedPrimary Granules: fewSecondary Granules: many orange, refractileN/C Ratio: 1.5:1

Size: 10-15µmNucleus: constricted but no threadlike filament; indentation >50% nucleusNucleoli: not visibleChromatin: coarse, clumpedPrimary Granules: fewSecondary Granules: abundant orange, refractileN/C Ratio: cytoplasm predominates

Size: 12-17µmNucleus: 2-5 lobes connected by thin filamentsNucleoli: not visibleChromatin: coarse, clumpedPrimary Granules: rareSecondary Granules: abundant orange, refractileN/C Ratio: cytoplasm predominates

IL-1, IL-6, IL-3

GM-CSFIL-3

GM-CSF, IL-3

GM-CSF,IL-5

GM-CSF,IL-5

GM-CSF,IL-5

Adapted from Harmening, 2009

Adapted from Carr & Rodk, 2013

Eosinophils are granulocytic leukocytes involved in the initiation and propagation of many inflammatory responses, including those of parasitic helminth infections and allergic

diseases (Harmening 2009;Hogan and Rothenberg 2006). There is some evidence that they may act as APCs. They have been implicated in hypersensitivity reactions including

allergic airway disease, asthma, eosinophilic gastritis and esophagitis, and Celiac disease (Hogan and Rothenberg 2006, Dyer, Foster et al. 2013)

They are produced and mature in the bone marrow and are released into the blood, where they migrate to mucosal beds such as the skin, GI tract, vagina, and bronchial mucosa (Harmening 2009). Evidence suggests they may have a role in preparing the

uterus for pregnancy and blastocyst implantation (Hogan and Rothenberg 2006).

Eosinophils have orange-staining secondary granules which contain several cytotoxic proteins capable of inducing tissue damage and dysfunction:

• Major Basic Protein – alters smooth muscle contraction responses and induces mast cell and basophil degranulation

• Eosinophil Cationic Protein – shown to possess antiviral activity; induction of mast cell degranulation, stimulation of airway mucus secretion, suppression of T cell

proliferation and IG synthesis by B cells• Eosinophil Peroxidase – catalyzes oxidation of several substances to produce highly

oxidative substances that promote cell death• Eosinophil-derived Neurotoxin – shown to possess antiviral activity (Hogan and

Rothenberg 2006)

• Eosinophils typically have up to 4 nuclear lobes.

• Hypersegmentation occurs when more than 3 eosinophils contain 5 lobes or 1 contains 6 or more lobes in a 100 cell differential (UVA).

• This is sometimes called a “right shift” (UVA).

• Hypersegmentation may accompany other disorders that affect maturation