P1253296655rMUvP

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Neutrophils, Eosinophils
Basophils
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Mast Cell
Basophil
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• BASOPHILS AND MAST CELL FUNCTION
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• Preformed granule content mediators
• 1. histamine
• -- blood vessel dilation
• -- lower blood pressure (shock)
• -- increased capillary permeability and blood
  leakage (edema)
• 2. acid mucopolysacchararides (e.g. heparin)
• 3. proteoglycans -- helps in the storage of
  histamine
• 4. cationic proteases
• 5. glycosidases
• 6. ECF-A eosinophilic chemotactic factor of
  analphylaxis

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BASOPHILS AND MAST CELL FUNCTION
B. Cyclooxygenase and lipoxygenase metabolite de
novo synthesis from PLA2 stimulation and
generation of arachidonic acid 1. LTC4 --
mediator involved in extreme inflammation
(SRS-A) 2. LTB4 -- chemoattractants and enhancer
(primer) of superoxide generation and granule
secretion by other granulocytes modifier of
suppressor and killer lymphocytes 3. PGD2
-- inhibits platelet aggregation chemokinetic
for neutrophils, w/ LTD4 mediates chemotaxis of
neutrophils enhances histamine release 4.
Eotaxin stimulates chemotaxis of eosinophils to
site of release 5. PAF- platelet activating
factor neutrophil chemoattratant, platelet
activator
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BASOPHILS AND MAST CELL FUNCTION
C. Cytokine release 1.Colony Stimulating
Factors -- GM-CSF 2. Interleukins -- IL-3,
IL-4, IL-6 3. IF 4. TNFa -- stored in
granules, particip. mast cell mediated
cytotoxicity -- constitutive
and stimulated release 5. Macrophage
Inflammatory Protein (MIP), and other
inflammation mediators 6. Broad spectrum of
activities is clonally based providing added
dimension of specificity
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EOSINOPHIL STRUCTURE  
A.   Size --9-15 ?m   B.    Number-- 200/ml
(vs. 2500 for lymphocytes)   C.  
Structure 1.     eosinophilic granules
1?m 2. peroxidase positive, especially in
rims 3. nucleus usually bi-lobed, virtually
never more than three lobes 4. lipid bodies
observed
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Neutrophils, Eosinophils
Basophils
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Basophil
Eosinophil
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EOSINOPHIL FUNCTION    

• SECRETION OF GRANULES
• 1. Eosinophil peroxidase not neutrophil
  peroxidase
• a) modest role in bacteriocidal response
• b) Eos have lower bacteriocidal activity than
  neuts
• c) prefers I or Br
• d) toxic even without peroxide
• e) potentiates effects of moncytes on bacteria
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• 2.     Catalase mitigator of superoxide/H2O2
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• 3. Peroxisome-like enzymes
• a) lipid oxidases -- enoyl-Co A hydratase, Acyl
  CoA oxidase
• 4. Lectins -- exist in crystalloids
•  

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EOSINOPHIL FUNCTION (contd)
A. SECRETION OF GRANULES (contd)
5. Basic proteins a) major basic protein (MBP)
constitutes the crystal core, toxic to parasites,
mammalian cells, induces histamine release from
basophils -- 55 of granule protein, MW 14kDa,
PI10.9 -- found deposited in placenta and
serum preterm -- releases adherence pads of
Eos -- damages Shistosomulae, Trichinellae,
Trypanosomes -- minimally damaging to
bacteria -- toxic to mammalian cells --
constricts smooth muscle -- activates
superoxide release from neuts   6. Cationic
protein (ECP) a) toxic to parasites b)
regulates lymphocyte proliferation c)
eosinophilic cationic protein -- makes
transmembrane pores - therfore acts like BPI d)
eosinophilic neurotoxin e) lysophopholipase -
7-10 of eosinophil protein form Leyden crystals
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• EOSINOPHIL FUNCTION(contd)
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• B. RECEPTORS
• 1. receptors for IgG, C1q, C3b (CR1), C3bi
  (CR3), C5a. IgE
• 2. CD4 ---gt reacts with lymphocyte chemotactic
  factors
• 3.     MHCII ---gt can present Ag to T cells
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• C. LIPID MEDIATOR METABOLISM PRODUCTION
• 1.     Mitigation function weak stimulation,
  low eosinophil s
• a)     neutralizing enzymes for histamine ,
  LTC4(SRS-C4,D4,E4), PAF
• b)    mast cell/basophil secretion inhibitors
• c)    hypohalides break down leukotrienes
• 2.     Inflammatory function strong
  stimulation high eos. s
• a)     massive MBP release
• b)    LTC4 release (not LTB4)
  (bronchoconstrictor, vasodilator)
• c)    15 hydroxyeicosatetranoic acid (15-HETE)
  chemotactic, neutrophil activator
• d)    PGE2 (edema, vasodilator)

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Eosinophil mediators
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