Table 1 Important eosinophil receptors and granules and their respective functions

Granule

Primary

CLC

Causes inflammation and stimulates Th2 cells, has lysophospholipase activity

Secondary (specific, crystalloid, crystalline, alpha)

Crystalline core

MBP

Neutralizes heparin, is bactericidal by changing the negative charge of lipid bilayer and disorganizing it, toxic for helminths and airway epithelium, activates complement system, stimulates basophil/mast cell for histamine secretion

GM-CSF

Eosinopoiesis induction

IL-4

Th2 and M2 polarization, IgE class switching, CCL11 secretion

Cathepsin D, hydrolase, glucuronidase

ECM degradation

Matrix

ECP ribonuclease

• Forms toxic pores on target cell membranes and is bactericidal, antiviral, anti-helminth

• Sends signals to other cells, degranulates mast cells

EPX (EPO)

Cytotoxic, generates reactive oxygen species (ROS) for oxidative damage

EDN ribonuclease

Possesses antiviral activity

IL-2

Crucial for the expansion of all T cells

IL-6 and APRIL

Support long-lived plasma cells and B cell development

IL-13

Helps IL-4 with M2 polarization and IgE class switching

IL-10

M2 polarization, immune cells’ suppression

IL-5, SCF

Eosinopoiesis, eosinophil activation, recruitment

IFN-γ

Th1 and M1 differentiation, CD8 + T cell stimulation, vessel normalization, antiviral, antibacterial, IL-12 production, tumor suppression

IL-12

Th1 differentiation, IFN-γ production by NK cells and Th1 cells, Th2 inhibition

TNF, IL-1β

Have strong proinflammatory activities

TGF-α

Promotes epithelial wound healing and cell proliferation

TGF-β

• Plus IL-4: Th9 differentiation

• Plus IL-2: Treg differentiation

• plus IL-6/IL-21: Th17 differentiation

Exacerbates tissue fibrosis

IgA class swithcing

Histaminase

Degrades histamine

Collagenase, elastase, catalase, esterase

ECM degradation

NGF, PDGF, VEGF, EGF

Growth factors for proliferation of various cells

CCL7 (MCP-3)

A potent chemoattractant for monocytes, eosinophils, basophils, DCs, NK and T cells

CXCL1 (Groα)

Neutrophil chemoattractant, involved in angiogenesis and tumorigenesis

CCL11 (eotaxin-1)

The most important eosinophil chemoattractant, induces piecemeal degranulation (PMD)

CCL13 (MCP-4)

A major eosinophil, basophil, monocyte, T cell chemoattractant

CCL3 (MIP-1α)

Attracts macrophages, lymphocytes, and eosinophils

CCL5 (RANTES), CXCL9, CXCL10 (IP-10), CXCL16

Secreted from activated eosinophil to recruit Th1, CD8 + T, and NK cells

CXCL12 (SDF-1)

A weak eosinophil chemoattractant

CCL17, CCL22

Th2 recruitment to tissue, Treg recruitment (CCL22)

CCL20 (MIP-3α)

Induces eosinophil migration and activation

CCL9 (MIP-1γ)

Recruits DCs and macrophages to Peyer’s patches

Lipid bodies

LTC4, LTD4, LTE4

Induce bronchoconstriction, mucus production, airway inflammation, eosinophil lineage commitment

PGE1, PGE2

Smooth muscle relaxant and vasodilator

TXB2

Vasoconstriction and platelet aggregation

15-HETE

Vasoconstriction and angiogenesis promotion

PAF

Eosinophil chemoattractant, increases LTC4 production and eosinophil adhesion

COX, 5-lipoxygenase, LTC4 synthase

Esterify arachidonic acids and produce eicosanoids such as PGs and LTs

Receptors

Cytokine and growth factor receptors

IL-2Rα/β (CD25/CD122)

Binds to IL-2 that activates eosinophils to release EPX and induces chemotaxis

IL-3Rα/β (CD123/CD131)

Binds to IL-3 that helps with eosinopoiesis

IL-4Rα/β (CD124/CD132)

Binds to IL-4 that activates eosinophils

IL-5Rα/β (CD125/CD131)

• IL-5Rα binds to IL-5

• IL-5Rβ transfers the signal

IL-9Rα/β (CD129/CD132)

Binds to IL-9 that promotes eosinophil, mast cell, Treg, Th17 growth

IL-13Rα1 (CD213a1)

Binds to IL-13 that promotes P-selectin expression on eosinophils

IFN-γR1 (CDw119)

Binds to IFN-γ which boosts eosinophil anti-tumor activity

TGF-βR1

Binds to TGF-β

TNFαR1 and 2 (CD120a, b)

Bind to TNF-α that delays eosinophil apoptosis

IL-10R^b

Binds to IL-10 cytokine family such as IL-22 (important in antimicrobial peptide production) and IFN-λ (antiviral)

IL-13Rα1 (CD213a1)

Binds to IL-13

IL-17 A/F R (IL-17RA/IL-17RC)

Bind to IL-17 A and IL-17F of Th17 to cause IL-1β and IL-6 production

IL-18R

Binds to IL-18 that increases LFA-1 and ICAM-1 expression

IL-23R (IL-23R/IL-12Rβ1)

Binds to IL-23 that increases IL-17RA expression and recruits eosinophils to lungs

IL-27R (gp130/WSX-1)

Binds to IL-27 that prolongs eosinophil survival by reducing apoptosis

IL-31R (IL-31RA/OSMRβ)

Binds to IL-31 that activates eosinophils

TSLPR

Binds to TSLP cytokine that modulates eosinophil survival and promotes eosinophilia

GM-CSFRα/β (CD116/CD131)

Binds to GM-CSF to help with eosinophil lineage commitment and survival

SCFR (KIT) (CD117)

Binds to SCF to help with eosinophil lineage commitment and survival

IL-25R and IL-33R (ST2)

Bind to IL-25 and IL-33 that modulate eosinophil survival and promote eosinophilia

Fc receptors

FcεRI

High-affinity IgE receptor that does not activate eosinophils

FcεRII (CD23)

Low-affinity receptor for IgE

FcγRII (CD32)

Binds to IgG and triggers eosinophil activation

FcαRI (CD89)

Binds to IgA and triggers eosinophil activation and prevents apoptosis

FcγRI (CD64), FcγRIII (CD16)

Not constitutively expressed, upregulated by IFN-γ, C5a, PAF

Adhesion receptors

Integrin

CD11/CD18 (LFA1)

Binds to ICAM-1 (CD54) and -2 (CD102) for infiltration in airways

CD11b/CD18 (CR3)

Binds to ICAM-1 and fibrinogen, binds to β−glucan to induce EDN release against fungi

CD11c/CD18 (CR4)

Binds to iC3b

CD49d/CD29 (VLA4)

Binds to VCAM-1 to carry out extravasation

Selectin

L-selectin (CD62L)

Binds to Sialyl Lewis X of GlyCAM-1, CD34, MadCAM-1 on endothelium for eosinophil tethering before integrin activation

Others

PSGL-1

Its Sialyl Lewis X (CD15s) binds to P-selectin (CD62P) and E-selectin (CD62E) on endothelium for eosinophil tethering before integrin activation

Inhibitory receptors

Siglec-8

Binds to sialic acid and induces eosinophil death

Secretory proteins

VAMP-2, -7, -8, STX-17

Located in granules and Sombrero vesicles, form SNARE complexes with STX-4 and SNAP-23, crucial for exocytosis and PMD

Syntaxin-4 (STX-4), SNAP-23

Located in plasma membrane, form SNARE complexes with VAMP-2, -7, -8, and STX-17, crucial for exocytosis and PMD

Pattern recognition receptors (PRRs)

TLR-1, -2, -4, -5, -6

Present on cell surface and detect bacterial proteins, lipoproteins, and polysaccharides

TLR-3, -7, -8, -9, -10

Present in endosome and detect viral nucleic acids

CLRs

Detect fungal components

RLRs

Present in cytosol to detect viral dsRNA

RAGE

Binds to HMGB1 and promotes eosinophilia

NLRs

Present in cytosol and detect bacterial peptidoglycan

Chemokine receptors

CCR1 (CD191)

Binds to CCL3 (MIP1α), CCL5 (RANTES), CCL7 (MCP3), PAF

CCR2 (CD192)

Binds to CCL7, CCL8 (MCP2)

CCR3 (CD193)

• Binds to eotaxins (CCL11, CCL24, CCL26) that greatly enhance eosinophil chemoattraction with IL-5

• Binds to CCL5 (RANTES), CCL13 (MCP4), CCL7, CCL8

CCR4 (CD194)

Binds to CCL17 and CCL22

CCR5 (CD195)

Binds to CCL1, CCL5, CCL7

CCR6 (CD196)

Binds to CCL20

CCR8 (CD198)

Binds to CCL1 that is bactericidal and recruits eosinophils

CCR9 (CD199)

Binds to CCL25

CXCR2 (CD182) (IL-8Rβ)

Binds to CXCL1

CXCR3 (CD183)

Binds to CXCL9, CXCL10

CXCR4 (CD184)

Binds to CXCL12

FPR1

Binds to microbial peptides that induces leukocyte chemotaxis

Complement receptors

CR1 (CD35)

Binds to C3b, C4b, iC3b, C1q to activate eosinophils

CR3 (CD11b/CD18)

Binds to iC3b and ICAM-1

C3aR, C5aR, CR4, CD103

Bind to complement components that activate and attract eosinophils

Eicosanoid receptors

CysLT1R, CysLT2R, LTB4R, PGD2R, PGE2R, PAFR, fMLPR

Bind to lipid mediators such as LTs and PGs

MHC-II

Plus CD80/86 or CD40

MHC-II presents T cells with antigen peptides and CD80/86 or CD40 provide co-stimulation

HLA-DR

Upregulated in activated eosinophils