International Journal of Scientific Research in Knowledge, 2(11), pp.

531-537, 2014
Available online at http://www.ijsrpub.com/ijsrk
ISSN: 2322-4541; 2014; Author(s) retain the copyright of this article
http://dx.doi.org/10.12983/ijsrk-2014-p0531-0537

Full Length Research Paper

Computational Prediction for the Binding Affinity of Interleukins 3 and 5 and GMCSF to Cell Surface Receptors on Human Eosinophils
Shahin Gavanji1*, Hassan Mohabatkar2
1

Young Researchers and Elite Club, Khorasgan Branch, Islamic Azad University, Khorasgan, Isfahan, Iran
Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan, Iran.
*Corresponding Author: shahin.gavanji@yahoo.com

Received 18 September 2014; Accepted 24 November 2014

Abstract. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a 14.477 kD glycoprotein comprising 144 amino
acids residues. The respective encoding gene is located on chromosome 5 in human. This protein stimulates proliferation and
differentiation of macrophages. N-terminally seventeen amino acid residues are serving as a signal peptide while, the rest of
127 amino acids, known to have therapeutics application, is termed Molgramostim. Previous studies have revealed a high
affinity of this protein for binding to a heterodimer receptor on surface of the cell. The respective receptor includes and
chains which the chain is similar to interleukins 3 and 5 receptors. Due to this similarity, interleukins 3 and 5 are capable to
compete with GM-CSF in binding to the shared receptor. In the present study, to evaluate the binding affinity of interleukins 3
and 5 and GM-CSF to the same receptor, a computational prediction study carried out using Modeller, Hex and Molegro
softwares. According to the results, interleukin 3 with -517.09 kJ/mole, interleukin 5 with -538.05 kJ/mole and GM-CSF with 606.17 kJ/mole energy could bind to the and chains of receptor. In the next step the two chains of the receptor were
separated and the affinity of each protein to both chains was studied. Based on the results the binding affinity of all three
considered proteins to chain of the protein was weaker than the binding to chain. The binding energy of interleukin 3,
interleukin 5 and GM-CSF to chain of receptors was -620.37 kJ/mole,-663.80 kJ/mole and -696.07 kJ/mole respectively.
According to the results, interleukin 3 and interleukin 5 strongly compete with GM-CSF in binding to cell surface receptors on
human eosinophils.
Keywords: Docking, GM-CSF, Interleukin, Receptor.

cytokines which are produced by macrophages

(Clutterbuck et al., 1987). Interleukin 3 (IL-3) and 5
(IL-5) are produced by T cells and some of their
activities
included
proliferation
stimulation,
differentiation and survival of myeloid hemopoietic
and also regulate the hematopoiesis and inflammation
(Kafert et al., 1999).
IL-3 binds to respective receptors at the cell
surface to stimulate the proliferation of early multipotential progenitors (Metcalf and Nicola, 1995).
Recombinant hIL-3 is widely applied for treatment of
thrombocytopenia (Denzlinger et al., 1993). IL-5, is
an important cytokine which is synthesized by
activated T-helper 2 cells (Adachi et al., 1995).
Understanding the regulatory mechanisms of this
protein may be helpful to explore effective ways for
the control of allergic diseases. It has been shown that
in disease like asthma the amount of GM-CSF, IL-3,
and IL-5 increased in the airways of patients. (Adachi
et al., 1995). Additionally GM-CSF and IL-3 are so
important in fighting with microbial pathogens

1. INTRODUCTION
One of the most important cytokine is human
granulocyte macrophage colony stimulating factor
(hGMCSF) which is secreted by macrophages, Tlymphocyte cells, mast cells, endothelial cells and
fibroblasts (Schwanke et al., 2009). This protein has
molecular weight of 14.477 kD comprises 144 amino
acids residues. Seventeen amino acids from the Nterminus of hGMCSF are serving as a signal peptide
while, the rest of 127 amino acids are known as
Molgramostim. This protein is also termed as CSF-2
and CSFa. hGM-CSF is an important therapeutic
cytokine which is used in the treatment of myeloid
leukemia, neutropenia and aplastic anemia diseases
(Armitage, 1985). Moreover, hGM-CSF increases the
effector functions of neutrophils, eosinophils and the
antigen-presenting ability of monocytes (Vadas et al.,
1983; Morrissey et al., 1987). Moreover, hGM-CSF
might increase anti-tumour responses (Hill et al.,
1993). Interleukins (ILs) are a group of soluble

531

Gavanji and Mohabatkar

Computational Prediction for the Binding Affinity of Interleukins 3 and 5 and GM-CSF to Cell Surface Receptors on
Human Eosinophils

(Banchereau et al., 2000; Thery and Amigorena, 2001;

Foti et al., 2004; Stout and Suttles, 2004; Hume,
2006). IL-5 stimulate production and release of
granule from eosinophils and participate in allergic
reactions and anti-parasite responses (Thery and
Amigorena, 2001; Foti et al., 2004).
The studies of gene knockout showed that although
these cytokines are not essential in maintaining
steady-state
populations
of
granulocytes,
macrophages, and eosinophils, they are required for
the accelerating production of these cells in
inflammation and infection. The receptor of these
cytokines consist of a ligand-specific
(GMR, IL-3R, and IL-5R
(Gearing
et al., 1989; Tavernier et al., 1991; Kitamura et al.,
1991; Hayashida et al., 1990) and a common subunit
(C) (Hayashida et al., 1990)
main ligand-binding subunit (Robb et al., 1995;
Murata et al., 1992) and the C subunit converts the
ligandso it is important for strength signaling (Kitamura et
al., 1991; Kitamura et al 1991(b); Hayashida et al.,
1990; Bagley et al., 1997). It is showed the three
cytokines compete for induction of cell proliferation
and survival through the same signal transduction
pathway in eosinophil cells and leukemic cell line TF1 (Adachi et al., 1995; Kitamura et al., 1991; Bagley
et al., 1995; Murata et al., 1992; Ohnishi et al., 1993).
The GM-CSF receptor was first defined using binding
of radioactive GM-CSF to mouse and human bone
marrow cells and cell lines (Park et al., 1986; Walker
et al., 1985). The GM-CSF receptor chain gene
(CSF2RA) occurs in the pseudoautosomal region of
the X and Y chromosomes at Xp22.32 in humans
(Gough et al., 1990; Rappold et al., 1992). The
common chain gene (CSF2RB) is on chromosome
22q12.2-13.1 in humans (Shen et al., 1992). In
humans the GM-CSF and IL-3 receptor chains are
closely linked (within 190 kb) in the pseudoauto
somal regions of the X and Y chromosomes (Kremer
et al., 1993).
The human
spanning about 44 kb (Nakagawa et al., 1994) as
GM-CSF receptor is expressed in different types of
cancer like acute myeloid leukemia, chronic myeloid
leukemia, melanoma, certain breast cancer cell lines
and the prostate (Baldwin et al., 1991; Baldwin et al.,
1989) simultaneous inhibition of expression of the c
subunit of the receptors for GM-CSF, IL-3, and IL-5
receptors might be lead to specifically inhibiting
growth and development of cancer cells. Most types
of myeloid progenitors and mature monocytes,
neutrophils, eosinophils, and dendritic cells have GMCSF receptors. In this study we bound GM-CSF, IL-3,
and IL-5 to their receptors and predicted the energy
of affinity on the basis of kJ/mole. And also we

observed the competition of GM-CSF, IL-3, and IL-5

in binding to Cell Surface Receptors on Human
Eosinophils. We determined the best form of GMCSF in order to bind to its receptor on Human
Eosinophils.
2. MATERIALS AND METHODS:
As The first step, amino acid sequences of the human
Granulocyte-macrophage colony-stimulating factor
(GM-CSF) (Genbank ID: 1437), its receptor
(Genbank ID: 1438 were), interleukin 3 (Genbank ID
3562 ) and interleukin 5 (Genbank ID: 3567) and
their receptor subunits (Genbank IDs: 1439 and 3568
for IL5- and IL3- receptors, 3563 IL3- and 1439
IL5-) were deduced from NCBI Entrez protein data
base (www.ncbi.nl,.nih.gov/). GM-CSF comprises
144 amino acid residues which 17 residues from its Cterminus are accounted as a signal peptide removable
from the mature structure of protein. Due to the lack
of crystal and three dimensional structure of IL3 and
IL5 and their receptors in Protein Data Bank (PDB) ,
we implemented online Server named PHYRE2
Protein
Fold
Recognition
Server
(www.sbg.bio.ic.uk/phyre2/). Furthermore, to predict
of three dimensional structure of IL3 and IL5 and
their receptors a comparative modeling was performed
by
utilizing
SWISS-MODEL
database
(swissmodel.expasy.org/). As GM-CSF, IL3, IL5 and
their receptors possess and chains, we designed
the chain and chain of the proteins separately.
2.1. Computational Molecular docking
Hex software calculates protein-ligand docking and
binding affinity (kcal/mol). Assuming the ligand
rigidity, it can bind to the pair subunit receptor by
using three dimensional structures of molecules.
Furthermore, docking and superposition program to
use spherical polar Fourier (SPF) correlations to
accelerate the calculations (Ritchie, 2003). Hex-6bwinis downloaded on to the system and the molecular
Interphase tool is opened. In this we measured the
Binding affinity (kcal/mol) GM-CSF, IL3, IL5 toward
their receptors on the basis of known experimental
data. And also we observed the binding differences of
the chain and chain. Finally we made a mutation
in Glutamic acid 21 and we replaced it with Arginine
by using Molegro softwares. As the result we could
enhance Binding affinity (kcal/mol) of GM-CSF
protein to chain of GM-CSF receptor.
3. RESULTS AND DISCUSSIONS
According to table 2, molecular docking analyses of
the
human
Granulocyte-macrophage
colony-

532

International Journal of Scientific Research in Knowledge, 2(11), pp. 531-537, 2014

stimulating factor (GM-CSF), interleukin 3 and

interleukin 5 and their receptors showed that these
proteins in silico condition bind to their receptors
with close energy values. Prediction of interaction
energies between ligand and receptor has been a major
challenge for molecular docking. The PDB structures
of (hGM-CSF) docked with its receptor with E
totals of -606.17 kJ/mole and in docking with chain
of GM-CSF receptor with E totals of -340.34
kJ/mole and with chain with E totals of-696.07
kJ/mole First we docked the IL3 and its receptor and

the binding affinity was equal to -517.09. Then we

docked IL3 with chain of IL3 receptor which the
energy was equal to -479.82 and with chain with E
totals of -620.37 Binding affinity of interleukin 5 with
its receptor was -538.05 And with and chain of its
receptors was-539.46 and -663.80 respectively (Table
1). At last we made a mutation in Glutamic acid 21
and we replaced it with by using Molegro program.
As the result we could enhance Binding affinity
(kcal/mol) of GM-CSF protein to chain of GM-CSF
receptor.

Table1: protein- protein interactions

No
1
2
3
4
5
6
7
8
9

E totals(kJ/mole)
-606.17
-340.34
-696.07
-517.09
-479.82
-620.37
-538.05
-539.46
-663.80

Interactions
hGM-CSF and hGM-CSF receptor
hGM-CSF and chain of GM-CSF receptor
hGM-CSF and chain of GM-CSF receptor
IL3 and its receptor
IL3 with chain of IL3 receptor
IL3 with chain of IL3 receptor
Interleukin 5 with its receptor
Interleukin5 with chain of Interleukin5 receptor
Interleukin5 with chain of Interleukin5 receptor

Table2: Summary of the binding and competition of IL-5, IL-3 and GM-CSF
Competition by
IL 5
Cell type

Eosinophils

Interleukin 5
Interleukin 3
GM-CSF
Receptors

Monocytes

Neutrophils

IL 3

GM-CSF

Receptor
expression

Interleukin 5
Interleukin 3
GM-CSF
Receptors
Interleukin 5
Interleukin 3
GM-CSF
Receptors

+
+

+
+
+

+
+
+

+
+
+

+
+

+
+

+
+

Data demonstrated that human eosinophil cells

express high affinity receptors for IL-5 and IL-3
while, GM-CSF compete with IL-5 in binding to those
receptors. The competition between IL-5, IL-3, and
GM-CSF on the surface of eosinophils is important to
understand the common activation properties of these
cytokines. Recent studies on eosinophil functions
have shown that IL-5 as well as IL-3 and GM-CSF
share the similar effects on: enhancement of
eosinophil superoxide production (Gregory et al.,
2003), antibody dependent killing of tumor cells (Paul
et al., 1997) and helminthes (Behm and Ovington,
2000),
degranulation of the cell (MartinezMoczygemba and Huston, 2001), survival ability of

the cell in vitro (Zheng et al., 2002; Miike et al.,

1999), conversion from a normodense to a hypodense
phenotype, phagocytosis(Tai et al., 1991), and the
biosynthesis of proteoglycans (Rothenberg et al.,
1988). Interactions with a common receptor complex,
implies one unifying mechanism. However, utilization
of
a
common
signal-transduction
pathway
downstream from the receptor remains to be explored.
The second implication of the present findings is that
the competition between IL-5, IL-3, and GM-CSF
may serve to limit eosinophil stimulation, thus
preventing the excessive release of oxygen products,
leukotrienes, and granule contents of these cytokines
with potentially harmful consequences to the host

533

Gavanji and Mohabatkar

Computational Prediction for the Binding Affinity of Interleukins 3 and 5 and GM-CSF to Cell Surface Receptors on
Human Eosinophils

(Lopez et al., 1992; Lopez et al., 1992b). The

competition for I-IL-5 binding to eosinophils hy 11,-3
and GM-CSF was partial even when testeadt high
concentrations of competitors. This may be duteo the
Association of some but not all IL-5 receptors with
IL-3 and GM-CSF receptors or to the existence of
eosinophil subpopulations expressing either IL-5specific receptorso, r IL-S-, ll,-:l-, and GM-CSFassociated receptors. Morphological and functional
differences are been noted in eosinophils generated
in vitro and in vivo (Tai et al., 1991).
The physical nature of the competition between IL5, IL-3 and GM-CSF is not yet known, but it may
reflect the relatedness of these three eosinophil growth
factors and their receptors. The relatedness between
IL-5, IL-3, and GM-CSF extends from the structure
and close localization of their genes on the long arm
of chromosome 5 (van Leeuwen et al., 1989) to the
structure of the mature polypeptides. The IL-5, IL-3,
and GM-CSF molecules have conserved features, in
particular an area of hydrophilic amino acids in the
COOH terminus, and their tertiary structure is
predicted to be highly conserved (Lin et al., 2000). It
is clear that while in eosinophils the cross-reaction is
most evident, in monocytes IL-3 and GM-CSF crosscompete (Kaushansky et al., 1992; Elliott et al., 1992)
but IL-5 is unable to compete, and on neutrophils
neither IL-5 nor IL-3 compete for GM-CSF binding .
It is apparent therefore that for inhibition to occur the
homologous receptor needs to be expressed (Table 2),
and the unique pattern of competition between IL-5,
IL-3, and GM-CSF is observed on eosinophils
because these cells express all three receptors.

in sputum from patients with bronchial asthma:

Contributions of interleukin-5 and granulocytemacrophage
colony-stimulating
factor.
American Journal of Respiratory and Critical
Care Medicine, 151: 618623.
Baldwin GC, Golde DW, Widhopf GF, Economou J,
Gasson JC. Identification and characterization
of a low-affinity granulocyte-macrophage
colony-stimulating factor receptor on primary
and cultured human melanoma cells. Blood,
78(1991)609-615.
Baldwin GC, Gasson JC, Kaufman SE, Quan SG,
Williams RE, Avalos BR, Gazdar AF, Golde
DW, DiPersio JF (1989). Nonhaematopoietic
tumor cells express functional GM-CSF
receptors. Blood, 73: 1033-1037.
Bagley CJ, Woodcock JM, Stomski FC, Lopez AF
(1997). The structural and functional basis of
cytokine receptor activation: lessons from the
macrophage
colonystimulating
factor,
interleukin-3 (IL-3) and IL-5 receptors. Blood,
89: 1471-1482.
Bagley CJ, Woodcock JM, Hercus TR, Shannon MF,
Lopez AF (1995) . Interaction of GM-CSF and
IL-3 with the common beta-chain of their
receptors. Journal of Leukocyte Biology, 57:
739746.
Banchereau J, Briere F, Caux C, Davoust J, Lebecque
S, Liu YJ, Pulendran B, Palucka K.
Immunobiology of dendritic cells. Annual
Review of Immunology. 18(2000) 767-811.
Behm CA, Ovington KS (2000). The Role of
Eosinophils in Parasitic Helminth Infections:
Insights from Genetically Modified Mice.
Parasitol Today, 16202-209.
Clutterbuck E, Shields JG, Gordon J, Smith SH, Boyd
A, Callard RE, Campbell HD, Young IG,
Sanderson CJ (1987). ecombinant human
interleukin 5 is an eosinophil differentiation
factor but has no activity in standard human B
cell growth factor assays. European Journal of
Immunology, 17:1743-1750.
Denzlinger C, Tetzloff W, Gerhartz HH, Pokorny R,
Sagebiel S, Haberl C, Wilmanns W (1993).
Differential activation of the endogenous
leukotriene biosynthesis by two different
preparations
of
granulocyte-macrophagecolony-stimulating factor in healthy volunteers.
Blood, 81: 20072013.
Elliott MJ, Moss J, Dottore M, Park LS, Vadas MA,
Lopez AF (1992). Differential binding of IL-3
and GM-CSF to human monocytes. Growth
Factors. 6: 15-29.
Foti M, Granucci F, Ricciardi-Castagnoli P (2004). A
central role for tissue-resident dendritic cells in

4. CONCLUSION
Different studies showed that various factors are
involve in growth and difrentiation of red and white
blood cells. Cytokines secreted from immune cells
like T lymphocyte and Macrophage play special role
in differentiation of blood cells.
Granolocyte
Macrophage cloning stimulating factor (GM-CSF) is
one of this factors which could stimulate growth of
granulocyte cells (neutrophil, eosinophil and basophil)
and macrophage. The results of this study showed that
there is a significant competition between interleukin
3, 5 and GM-CSF in attaching to eosinophil receptors.
REFERENCES
Armitage JO (1985). Emerging applications of
recombinant human granulocyte-macrophage
colony-stimulating factor. EMBO Journal, 4:
25752581.
Adachi T, Motojima S, Hirata A, Fukuda T, Makino S
(1995). Eosinophil viability-enhancing activity

534

International Journal of Scientific Research in Knowledge, 2(11), pp. 531-537, 2014

innate responses. Trends in Immunology. 25:

650-654.
Gregory B, Kirchem A, Phipps S, Gevaert P, Pridgeon
C, Rankin SM, Robinson DS (2003).
Differential Regulation of Human Eosinophil
IL-3, IL-5, and GM-CSF Receptor -Chain
Expression by Cytokines: IL-3, IL-5, and GMCSF Down-Regulate IL-5 Receptor
Expression with Loss of IL-5 Responsiveness,
but Up-Regulate IL-3 Receptor Expression.
Journal of Immunology, 17: 5359-5366.
Gearing DP, King JA, Gough NM (1989). Expression
cloning of a receptor for human granulocytemacrophage colony-stimulating factor. EMBO
Journal, 8: 3667-3676.
Gough NM, Gearing DP, Nicola NA, Baker E,
Pritchard M, Callen DF, Sutherland GR (1990).
Localization of the human GM-CSF receptor
gene to the X-Y pseudoautosomal region.
Nature, 345: 734-736.
Hill AD, Redmond HP, Naama HA, Bouchier-Hayes
D (1993). Granulocyte-macrophage colonystimulating factor inhibits tumor growth. British
Journal of Surgery, 80:15431546.
Hayashida K, Kitamura T, Gorman DM, Arai K,
Yokota T, Miyajima A (1990). Molecular
cloning of a second subunit of the receptor for
human
granulocyte-macrophage
colonystimulating factor (GM-CSF): reconstitution of a
high-affinity GM-CSF receptor. Proceedings of
the National Academy of Sciences of the United
States of America, 87: 9655-9659.
Hume DA (2006). The mononuclear phagocyte
system. Current Opinion in Immunology, 18:
49-53.
Kafert S, Luther S, Bll I, Wagner K, Ganser A, Eder
M (1999). Functional Analysis of a Single
Chain Chimeric a/b-Granulocyte-Macrophage
Colony-stimulating Factor Receptor. Journal of
Biological Chemistry, 274: 3306433071.
Kitamura T, Sato N, Arai K, Miyajima A (1991).
Expression cloning of the human IL-3 receptor
cDNA reveals a shared beta subunit for the
human IL-3 and GM-CSF receptors. Cell, 66:
11651174.
Kaushansky K, Shoemaker SG, Broudy VC, Lin NL,
Matous JV, Alderman EM, Aghajanian JD,
VanDyke PJ, Pearce MK (1992). Structurefunction relationships of interleukin-3. An
analysis based on the function and binding
characteristics of a series of interspecies
chimera of gibbon and murine interleukin-3.
Journal of Clinical Investigation, 90: 1879
1888.
Kitamura T, Takaku F, Miyajima A (1991). IL-1
upregulates the expression of cytokine receptors

on a factor-dependent human hemopoietic cell

line, TF-1. International Immunology, 3: 571
577.
Kremer E, Baker E, D'Andrea RJ, Slim R, Phillips H,
Moretti PA, Lopez AF, Petit C, Vadas MA,
Sutherland GR (1993) . Sutherland, A cytokine
receptor
gene
cluster
in
the
X-Y
pseudoautosomal region?. ,Blood, 82: 22-28.
Lopez AF, Elliott MJ, Woodcock J, Vadas MA
(1992). GM-CSF, IL-3 and IL-5: crosscompetition on human haemopoietic cells.
Immunology Today, 13: 495-500.
Lopez AF, Vadas MA, Woodcock JM, Milton SE,
Lewis A, Elliott MJ, Gillis D, Ireland R, Olwell
E, Park LS (1992). Interleukin-5, interleukin-3,
and granulocyte-macrophage colony-stimulating
factor cross-compete for binding to cell surface
receptors on human eosinophils. Journal of
Biological Chemistry, 266: 24741-7.
Lin YH, Huang CJ, Chao JR, Chen ST, Lee SF, Yen
JJ, Yang-Yen HF (2000). Coupling of
Osteopontin and Its Cell Surface Receptor
CD44 to the Cell Survival Response Elicited by
Interleukin-3
or
Granulocyte-Macrophage
Colony-Stimulating Factor. Molecular and
Cellular Biology, 20: 27342742.
Muto A, Watanabe S, Miyajima A, Yokota T, Arai K
(1995). High affinity chimeric human
granulocyte-macrophage
colony-stimulating
factor receptor carrying the cytoplasmic domain
of the beta subunit but not the alpha subunit
transduces growth promoting signals in Ba/F3
cells. Biochemical and Biophysical Research
Communications, 208: 368-375.
Murata Y, Takaki S, Migita M, Kikuchi Y, Tominaga
A, Takatsu K (1992). Molecular cloning and
expression of the human interleukin 5 receptor.
Journal of Experimental Medicine, 175: 341
351.
Morrissey PJ, Bressler L, Park LS, Alpert A, Gillis S
(1987).
Granulocyte-macrophage
colonystimulating factor augments the primary
antibody response by enhancing the function of
antigen presenting cells. Journal of Immunolog,
139 : 11131119.
Metcalf D, Nicola NA (1995). The Hemopoietic
Colony-stimulating Factors: From Biology to
Clinical Applications. Cambridge University
Press.
Miike S, Nakao A, Hiraguri M, Kurasawa K, Saito Y,
Iwamoto I (1999). Involvement of JAK2, but
not PI 3-kinase/Akt and MAP kinase pathways,
in anti-apoptotic signals of GM-CSF in human
eosinophils. Journal of Leukocyte Biology, 65:
700-706.

535

Gavanji and Mohabatkar

Computational Prediction for the Binding Affinity of Interleukins 3 and 5 and GM-CSF to Cell Surface Receptors on
Human Eosinophils

Martinez-Moczygemba M., Huston D.P (2001).

Proteasomal regulation of c signaling reveals a
novel mechanism for cytokine receptor
heterotypic desensitization. Journal of Clinical
Investigation, 108: 1797-1806.
Nakagawa Y, Kosugi H, Miyajima A, Arai K, Yokota
T (1994). Structure of the gene encoding the
alpha subunit of the human granulocytemacrophage colony stimulat-ing factor receptor.
Implications for the evolution of the cyto-kine
receptor superfamily. Journal of Chemical
Biology, 269: 10905-10912.
Ohnishi T, Sur S, Collins DS, Fish JE, Gleich GJ,
Peters SP (1993). Eosinophil survival activity
identified as interleukin-5 is associated with
eosinophil recruitment and degranulation and
lung injury twenty-four hours after segmental
antigen lung challenge. Journal of Allergy and
Clinical Immunology, 92: 607615.
Park LS, Friend D, Gillis S, Urdal DL (1986).
Characterization of the cell surface receptor for
granulocyte- macrophage colony-stimulating
factor. Journal of Chemical Biology, 261: 41774183.
Paul CC, Mahrer S, McMannama K, Baumann MA
(1997). Autocrine activation of the IL-3/GMCSF/IL-5 signalling pathway in leukemic cells.
American Journal of Hematology, 56: 7985.
Rappold G, Willson TA, Henke A, Gough NM
(1992). Arrangement and localization of the
human GM-CSF receptor alpha chain gene
CSF2RA within the X-Y pseudoau- tosomal
region. Genomics, 14: 455-461.
Rothenberg ME, Pomerantz JL, Owen WF Jr,
Avraham S, Soberman RJ, Austen KF, Stevens
RL (1988). Characterization of a human
eosinophil proteoglycan, and augmentation of
its biosynthesis and size by interleukin 3,
interleukin 5, and granulocyte/macrophage
colony stimulating factor. Journal of Biological
Chemistry. 263: 13901-8.
Ritchie DW (2003). Evaluation of Protein Docking
Predictions Using Hex 3.1 in CAPRI Rounds 1
and 2. PROTEINS : Structure, Function, and
Bioinformatics. 52: 98-106.
Robb L, Drinkwater CC, Metcalf D (1995).
Hematopoietic and lung abnormalities in mice
with a null mutation of the common -subunit of
the receptors for granulocyte-macrophage
colony-stimulating factor and interleukins 3 and
5. Proceedings of the National Academy of
Sciences of the United States of America, 92:
9565-9569.

Stout RD, Suttles J (2004). Functional plasticity of

macrophages: reversible adaptation to changing
microenvironments. Journal of Leukocyte
Biology. 76: 509-513.
Shen Y, Baker E, Callen DF, Sutherland GR, Willson
TA, Rakar S, Gough NM (1992). Localization
of the human GM-CSF receptor beta chain gene
(CSF2RB) to chromosome 22q12.2-q13.1,
Cytogenet. Cell Genet, 61: 175-177.
Schwanke RC, Renard G, Chies JM, Campos MM,
Batista EL Jr, Santos DS, Basso LA (2009).
Molecular cloning, expression in Escherichia
coli and production of bioactive homogeneous
recombinant
human
granulocyte
and
macrophage
colony
stimulating
factor.
International
Journal
of
Biological
Macromolecules, 45: 97102.
Tai PC, Sun L, Spry CJ (1991). Effects of IL-5,
granulocyte/macrophage
colony-stimulating
factor (GM-CSF) and IL-3 on the survival of
human blood eosinophils in vitro. Clinical &
Experimental Immunology, 85: 312316.
Tavernier J, Devos R, Cornelis S, Tuypens T, Van der
Heyden J, Fiers W, Plaetinck G (1991). human
high affinity interleukin- 5 receptor (IL5r) is
composed of an IL5-CSF.
Cell, 66: 1175-1184.
Thery C, Amigorena S (2001). The cell biology of
antigen presentation in dendritic cells. Current
Opinion in Immunology, 13: 45-51.
Vadas MA, Nicola NA, Metcalf D (1983). Activation
of
antibody
dependent
cell mediated
cytotoxicity of human neutrophils and
eosinophils by separate colony stimulating
factors. Journal of Immunolog, 130:795799.
van Leeuwen BH, Martinson ME, Webb GC, Young
IG (1989). Molecular organization of the
cytokine gene cluster, involving the human IL3, IL-4, IL-5, and GM-CSF genes, on human
chromosome 5. Blood, 73: 1142-8.
Walker F, Burgess AW (1985). Specific binding of
radioiodinated
granulocyte-macrophage
colony-stimulating factor to hemopoietic cells.
EMBO Journal, 4: 933939.
Zheng X, Karsan A, Duronio V, Chu F, Walker DC,
Bai TR, Schellenberg RR (2002). Interleukin-3,
but not granulocyte-macrophage colonystimulating factor and interleukin-5, inhibits
apoptosis of human basophils through
phosphatidylinositol 3-kinase: requirement of
NF-B-dependent and -independent pathways.
Immunology, 107: 306-315.

536

International Journal of Scientific Research in Knowledge, 2(11), pp. 531-537, 2014

Shahin Gavanji graduated in Biotechnology at MSc at the Department of Biotechnology, Faculty of

Advanced Sciences and Technologies, University of Isfahan, Isfahan, Iran. He has over 10
international medals in invention. Shahin Gavanji's research has focused on Pharmacy and
Pharmacology, Nano Biotechnology, Bioinformatics, Biotechnology - Medical Biotechnology. He is
editor in chief of International Journal of Scientific Research in Inventions and New Ideas.

Dr. Hassan Mohabatkar is a faculty member at Department of Biotechnology, Faculty of Advanced

Sciences and Technologies, University of Isfahan, Isfahan, Iran. His research has focused on
Bioinformatics.
h_mohabatkar@yahoo.com

537