maturation of eosinophil

1. Maturation of
Eosinophil
Soofia Yaqub
10060614-011

2. Eosinophil
• Definition:
A type of white blood cell (leukocyte)
containing uniformly-sized, coarse round
cytoplasmic granules that are easily stained by
eosin or other acid dyes, it is a granular
leukocyte having a nucleus with two lobes
connected by a thread of chromatin.

3. Function of eosinophil
• The functions of the eosinophil are varied, some of
which are very similar to other white blood cells
• The eosinophil is a specialized cell of the immune
system
• Eosinophils may have a physiological role in organ
formation (e. g. postgestational mammary gland
development).
• Movement to inflamed areas, trapping substances,
killing cells, antiparasitic and bactericidal activity,
participating in immediate allergic reactions, and
modulating inflammatory responses.

4. Structure of eosinophil
• The eosinophil generally has a nucleus with
two lobes (bilobed), and cytoplasm filled with
approximately 200 large granules containing
enzymes and proteins

5. Location of eosinphil
• Eosinophils are normal cellular component of
the blood and also of certain tissues, including
spleen, lymph nodes, thymus, and the
submucosal areas of the gastrointestinal,
respiratory, and genitourinary tracts. Counts
of 0 to 450 eosinophils per cubic millimeter of
blood are generally considered within normal
limits.

6. Maturation of eosinophil
• Eosinophil – a granulocyte develop from stem cell
(CD34+) in bone marrow, under the influence of
cytokines, IL-3, GM-CSF and IL-5.
• IL-3 (interleukin-3)-proliferation and
differentiation of stem cells to the multipotent
myeloid and eosinophil progenitor cells
• GM-CSF (granulocyte macrophage colony
stimulating factor)- same as IL-3
• IL-5 (interleukin-5)- expansion, terminal
differentiation and functional activation of
eosinophils

7. Maturation of eosinophil
• The stages in the normal maturation of the
eosinophil are: myeloblast, promyelocyte,
myelocyte ,metamyelocyte, band cell and
segmented cell.

8. Myeloblast
• Size. Fifteen to 20 microns in diameter.
• Nucleus. The nucleus is round or ovoid and stains predominantly
reddish-purple. The interlaced chromatin strands are delicate, well
defined, and evenly stained. Two or more pale blue nucleoli are
demonstrable. The nucleus occupies most of the cell with a
nucleus-cytoplasm ratio of 6:1. It is separated from the cytoplasm
by a definite nuclear membrane.
• Cytoplasm. The cytoplasm is a narrow, deep blue, nongranular rim
around the nucleus.

9. Promyelocyte.
• Size. Fifteen to 21 microns in diameter.
• Nucleus. The nucleus is round or ovoid with coarse-clumping,
purple chromatin material. One to three oval, light-blue
nucleoli are usually present. The nucleoli are less distinct than
in the myeloblast. This cell has a nucleus-cytoplasm ratio of
4:1.
• Cytoplasm. The cytoplasm is light purple and contains varying
numbers and sizes of dark nonspecific granules that stain red
to purplish-blue. The granules usually overlie the nucleus.

10. Myelocyte
• In the myelocytic stage the granules are definite and so
numerous ,the differentiation is generally considered as
first occurring in the myelocytic stage.
• The earliest eosinophil (myelocyte) has a few dark
spherical granules with reddish tints that develop among
the dark, nonspecific granules.
• The nucleus of the myelocyte remains somewhat round to
oval and the chromatin material is more closely clumped

11. Metameylocye
• This cell closely resembles the myelocyte.
• The nucleus is indented and often resembles a
kidney bean.
• Nucleoli are not present and the nuclear
chromatin material is coarser and clumped.
• Cytoplasmic granules are also present.

12. Band cell
• This cell has a horseshoe shaped nucleus.
• The opposite sides of the nucleus are more or less parallel.
• This cell may be differentiated from the metamyelocyte by the
nuclear shape and the tendency for the nuclear sides to
become parallel.
• The nuclear chromatin material is markedly clumped.
Eosinophil band cell

13. Mature Segmented cells
• Size. Ten to 15 microns in diameter.
• Nucleus. The nucleus has definite lobes separated by a very
narrow filament or strand. Seldom does an eosinophil have
more than two lobes.
• Cytoplasm. The cytoplasm contains bright reddish-orange,
distinct granules. The granules are spherical, uniform in size,
and evenly distributed throughout the cytoplasm, but rarely
overlie the nucleus.

14. Myeloblast- PromyelocyteMyelocyteMetamyelocyte Band Eosinophil

15. Maturation of eosionophil

16. Development of eosinophil
• Eosinophils are formed exclusively in the bone
marrow where they spend about 8 days in the
process of maturation before moving into the
blood vessels. They travel through the vessels for
8 to 12 hours before they finally arrive at
destination tissues, where they remain for 1 to 2
weeks. Interleukin 5 (IL-5) is a major growth
factor for this type of cell.
• Eosinophil are differentiated from myeloid
precursor cell in response to different cytokines.

17. Migration and activation
• Eosinophils produce and store many secondary granule
proteins prior to their exit from the bone marrow.
• After maturation, eosinophils circulate in blood and
migrate to inflammatory sites in tissues
• To sites of helminth infection in response to
chemokines like CCL11 (eotaxin-1), CCL24 (eotaxin-2),
CCL5 (RANTES), and certain leukotrienes like
leukotriene B4 (LTB4) and MCP1/4.
• At these infectious sites, eosinophils are activated by
Type 2 cytokines released from a specific subset of
helper T cells (Th2), and IL-3 are important for
eosinophil activation as well as maturation

18. Role of IL-5
• IL-5 eosinophil is a recruitment, proliferation, maturation,
maintenance and activation factor
• Bone marrow cultures with IL-3 and GM-CSF produce very
few eosinophil colonies. T-cell derived IL-5 is required.
• IL-5 is a heterogeneous glycoprotein 32 - 62kDa. Gene on
the long arm of chromosome 5, along with the other
haematopoetic growth factors GM-CSF, IL-3, IL-4.
• IL-5 enhances phagocytic activity, stimulates superoxide
production, upregulates IgG and IgE Fc and complement
receptors, delays apoptosis - prolongs eosinophil survival
• Humanised monoclonal anti-IL-5 decreases circulating
eosinophils

19. Eosinophil specific proteins
• The cytoplasmic granules are membrane bound and contain a
• crystalloid protein core. The granule and cell membranes fuse
• on triggering and release the granule contents.
The granules contain four highly toxic arginine-rich proteins with a
high isoelectric point pH > 11.0
• major basic protein (MBP),
• eosinophil cationic protein (ECP),
• eosinophil peroxidase (EPO),
• eosinophil-derived neurotoxin (EDN).
These bind the negatively charged surfaces of parasites.
Their extracellular release may cause dysfunction and destruction of
surrounding cells.
• Eosinophils also produce IL-4, IL-5 and Eotaxin.

20. Eosinophil adhesion
• Eosinophils need to move to sites of inflammation and
adhere to and cross pulmonary vascular epithelial
cells.
• Adhesion :
The alpha-4 integrin (very late activation
antigen) VLA-4 on eosinophils binds to the adhesion
molecule VCAM-1 on vascular endothelium.
• Transmigration :
The beta-2 integrin p-selectin on eosinophils
binds to its ligand ICAM-1 on vascular endothelium

21. Eosinophil : pathogenic role in allergy
• Eosinophils abundant in allergic sites
• ECP / MBP cause damage and denudation of
bronchial epithelium, and can cause impairment
of ciliary beating. Seen in biopsy of asthma
• Serum and bronchial lavage / sputum ECP levels
raised in :
• asthmatics
• seasonal hay fever
• experimental asthma challenge
• IL-5 KO mice lack bronchial hyper-reactivity

22. Eosinophil : resolution of inflammation
• Apoptosis - eosinophils retain granules but lose
the ability to secrete them. Apoptotic eosinophils
are ingested and digested by macrophages in a
non-inflammatory process.
• Steroid treatment - very effective for eosinophil-
mediated diseases.
• Prevents transcription of eosinophil cytokines
• Accelerates eosinophil apoptosis
• Downregulates VCAM-1

23. References
• http://medical-dictionary.thefreedictionary.com/eosinophil (2)
• http://www.free-https://re
• gid.org/discover/what-eosinophil (3-5)
http://onlinelibrary.wiley.com/doi/10.1002/eji.200526242/pdf (6)
• ed.net/sweethaven/MedTech/Hematology/lessonMain.asp?iNum=0406 (7-
13)
• http://www.cincinnatichildrens.org/service/c/eosinophilic-
disorders/conditions/eosinophil/ (16)
• immuneweb.xxmu.edu.cn/guowaippt/Glasgow/mcsharryeosinophils.ppt (17-
22)