Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
Eosinophils are derived from CD34+ progenitor cells (same as mast cells) and their development is influenced by IL-5. Eosinophils migrate to tissues in response to RANTES (CCL-5) and eotaxin (CCL-11, CCL-24).
CD differentiation (captions in German). Image source: Wikipedia.
Blood cell lineage. Image source: Wikipedia.
Eosinophil. Image source: Wikipedia.
Eosinophil. Image source: Wikipedia.
Eosinophils have:
- primary granules or eosinophil-specific granules (with Charcot-Leyden crystal protein)
- secondary granules (200/cell)
- lipid bodies which store arachidonic acid
Mediators from Eosinophils
Major Basic Protein (MBP)
MBP is a very alkaline protein which makes half of all the eosinophil granule protein. It is cytotoxic to parasites just as EDN and ECP are (see below). MBP and eosinophils are increased in the bronchoalveolar lavage (BAL) fluid of patients with asthma and correlate with disease activity. MBP triggers histamine release from mast cells/basophils.
Eosinophil-derived Neurotoxin (EDN)
EDN is a single-chain polypeptide which is, contrary to its name, not specific to eosinophils. Cytototic to parasites, same as MBP and ECP.
Eosinophil Cationic Protein (ECP)
ECP is another basic protein (similar to MBP) in the eosinophil specific granules. Cytototic to parasites, same as MBP and EDN.
Eosinophil Peroxidase (EPO)
EPO is similar to neutrophil myeloperoxidase (MPO) and contributes to local inflammation.
Cytokines and Lipid Mediators
Eosinophils produce many cytokines, chemokines, and growth factors: IL-2-6, 8, 10, GM-CSF, TGF, TNF. Eosinophils also metabolize arachidonic acid to leukotrienes, prostaglandins and thromboxane B2.
TNF-α may play an important role in severe refractory asthma unresponsive to inhaled CS. Etanercept (Enbrel) is a recombinant human TNF-α receptor fusion protein (anti-TNF-α). Its therapeutic potential is based on the fact that TNF-alpha is the "master regulator" of the inflammatory response in many organ systems.
Mediators from eosinophils are remembered by the mnemonic CML EEE:
Cytokines
MBP
Lipid Mediators
EDN
ECP
EPO
Mediators from eosinophils.
What is the most potent chemokine (chemoattractant) for eosinophils?
(A) IL-5
(B) IL-8
(C) LTB4
(D) eotaxin
(E) IL-4
(F) IL-13
Answer: D.
Eosinophil chemotactic protein 2 (Eotaxin-2) is the most potent chemoattractant for eosinophils but IL-5 is the most specific stimulant of their production. Eosinophils migrate to tissues in response to RANTES (CCL-5) and eotaxin (CCL-11, CCL-24).
The receptors for IL-3, IL-5, and GM-CSF share a common β chain. All 3 cytokines stimulate the development of eosinophils.
The receptors for IL-3, IL-5, and GM-CSF share a common β chain. All 3 cytokines stimulate the development of eosinophils.
References
Allergy and Immunology MKSAP, 3rd edition.
Hypereosinophilic syndromes. Orphanet Journal of Rare Diseases 2007, 2:37doi:10.1186/1750-1172-2-37.
Targeting TNF-α: A novel therapeutic approach for asthma. JACI, Volume 121, Issue 1, Pages 5-10 (January 2008).
Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma. NEJM, Volume 360:973-984 March 5, 2009 Number 10.
Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia. NEJM, Volume 360:985-993 March 5, 2009 Number 10.
Immunomodulators for allergic respiratory disorders. Casale TB, Stokes JR. J Allergy Clin Immunol. 2008 Feb;121(2):288-96; quiz 297-8.
Mind Maps: Immunomodulators for allergic disorders
Related Reading
FIT Corner Q & A from 5th edition of Cellular and Molecular Immunology, edited by Abul K. Abbas and Andrew H. Lichtman. ACAAI, 2004.
Serum eosinophil granule proteins predict asthma risk in allergic rhinitis. Nielsen LP, Peterson CG, Dahl R. Allergy. 2008 Dec 24.
Published: 12/13/2007
Updated: 08/05/2010
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