monocyte chemoattractant protein 1(mcp-1)
TRANSCRIPT
MONOCYTE CHEMOATTRACTANT PROTEIN -1 (MCP-1) AS A
BIOMARKER
By:-Pratik K. Kamu PC/2014/209 Guided By:-Dr.D.Sujatha
Contents
Definition and characteristics of biomarker
What is MCP-1
Site of production of MCP-1
Methods and normal levels
Mechanisms and pathways
Role of MCP-1 as a biomarker in various diseases
Conclusion205/02/2023
Definition Of Biomarker
Biological markers (biomarkers) have been defined as
“cellular, biochemical or molecular alterations that are
measurable in biological media such as human tissues, cells,
or fluids.”
In practice, biomarkers include tools and technologies that
can aid in understanding the prediction, cause, diagnosis,
progression, regression, or outcome of treatment of disease.
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Characteristics of an ideal biomarkerStandardized
High sensitivity and specificity
Accurate
Reproducible
Easy to interpret
Acceptable to patients
Consistent and cost effective
Have an impact on clinical/risk management405/02/2023
MCP-1Chemokines constitute a family of chemoattractant cytokines and are subdivided into four families on the basis of the number and spacing of the conserved cysteine residues in the N-terminus of the protein.
Chemokines play a major role in selectively recruiting monocytes, neutrophils, and lymphocytes, as well as in inducing chemotaxis through the activation of GPCRs.
Both CCL2 and its receptor CCR2 have been demonstrated to be induced and involved in various diseases.
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Chemokine receptors & their ligandsFamily Systematic name Human ligand Chemokine
receptor
C Chemokine(γ chemokine)
CCL2CCL3CCL5
MCP-1, MCAFMIP-1α, LD78α
RANTES
CCR2CCR1, CCR5CCR1, CCR5
CC Chemokine(β chemokine)
CCL13CCL14
MCP-4HCC-1
CCR1, CCR2, CCR3CCR1
CXC Chemokine(α chemokine)
CXCL8CXCL9
IL-8MIG
CXCR1, CXCR2CXCR3-A, CXCR3-B
CX3C Chemokine(δ chemokine)
CX3CL1 Fractalkine CX3CR1
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Structure of MCP-1
Satish L. Deshmane et al Journal of Interferon & Cytokine Research ,Volume 29, Number 6, 2009 , 315705/02/2023
Continued
The monocyte chemoattractant protein-1(MCP-1/CCL2) is a member of the C-C chemokine family, and a potent chemotactic factor for monocytes.
MCP-1 is believed to be identical to JE , a gene whose expression is induced in mouse fibroblasts by platelet-derived growth factor.
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Site of production of MCP-1CCL2 is:
• A monomeric polypeptide, with a molecular weight of
approximately 13 kDa.
• Anchored in the plasma membrane of endothelial cells by
glycosaminoglycan side chains of proteoglycans.
• Primarily secreted by monocytes ,macrophages and dendritic
cells.
Platelet derived growth factor is a major inducer of CCL2 gene.
To become activated CCL2 protein has to be cleaved by
metalloproteinases i.e. MMP-12. 905/02/2023
Mechanism and pathways of monocyte recruitment
CCL2 has been demonstrated to recruit monocytes into foci of active
inflammation in this regard, evidence has been provided describing the
involvement of prostaglandin E2 in the attraction of monocytes to the
site of inflammation and their maturity into macrophages.
In addition to CCL2, several other chemokines were also shown to be
involved in the recruitment of monocytes. In this regard, it has been
demonstrated that the stimulation of RANTES leads to recruitment
monocytes.1005/02/2023
Normal levels and methods of measurement of MCP-1
MCP-1 in serum - 125±42
pg/ml
uMcp-1/U.cr - 9.8±6.7
pg/mg
Sandwich enzyme-linked immunosorbent assay (ELISA)
& qPCR .
Priyanka et al, International journal of diabetes mellitus 2(2010)15-191105/02/2023
Involvement of CCL2 in different diseasesEffects Mechanism References
Thrombus formation By generating tissue factor Charo and Taubman 2004
Oxygen-induced injury (retinopathy)
Marked increase in CCL2 in microglia/macrophages
Davies and others 2006
Inflammatory bowel disease
CCL2-mediated differentiation ofintestinal macrophages
Spoettl and others 2006
Allergic asthma IL-4 and IL-13-induced release of CCL2 inbronchial epithelium
Ip and others 2006
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Role of MCP-1 in diabetic nephropathy
In the kidney, this can lead to the development of an innate
immune response which is predominantly characterized by the
accumulation of kidney macrophages .
Studies in human and experimental diabetic nephropathy have
shown that kidney macrophage accumulation is associated with
the progression of diabetes ,the development of renal injury and
kidney fibrosis and the decline in renal function, suggesting that it
is an inflammatory-mediated disease
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Role of MCP-1 in diabetic nephropathy
G. H. Tsche1,2 am J physiol renal physiol 294: F697–F701, 2008. 1405/02/2023
Role of MCP-1 in cardiovascular diseases
MCP-1 (monocyte chemotactic protein-1) plays a critical role in the development of cardiovascular diseases.
MCP-1, by its chemotactic activity, causes diapedesis of monocytes from the lumen to the sub endothelial space where they become foam cells, initiating fatty streak formation that leads to atherosclerotic plaque formation.
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Role of MCP-1 in cardiovascular diseases
Jianli niu and pappachan e. Kolattukudy clinical science (2009) 117, 95–109 1605/02/2023
Role of MCP-1 in cancerChemokines are involved in a broad array of normal host activities
that impact cancer; therefore, it is possible that they will be found
to have important effects on cancer pathogenesis.
Because of their ability to attract and activate lymphocytes, some
chemokines might be expected to stimulate host antitumor
responses.
Some of the chemokines are known to possess angiogenic
activities, which could potentially contribute to tumor growth and
progression.
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Role of MCP-1 in cancer
I. Conti, B.J. Rollins , Seminars in Cancer Biology 14 (2004) 149–154 1805/02/2023
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CCR2 Antagonists
CAS 445479-97-0RS 504393Highly selective CCR2 chemokine receptor antagonistBMS CCR2 22High affinity, potent CCR2 antagonistINCB 3284 dimesylateSelective CCR2 antagonist
Conclusion
CCL2 remains one of the most studied of the chemokines.
Urinary levels of MCP-1 can be monitored as a marker of
diabetic renal inflammation, and this may prove to have
significant diagnostic value in assessing the effectiveness of novel
or combined therapies.
Drugs which block several upregulated chemokine receptors,may
prove to be very effective.
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Naylor S. Biomarkers: current perspectives and future prospects. Expert Rev Mol Diagn 3: 525–529, 2003.
Schulte PA. A conceptual and historical framework for molecular epidemiology. In: Molecular epidemiology: principles and practices (Schulte PA, Perera FP, eds), pp 3–44. San Diego: Academic Press, 1993.
Niu J. "Role of MCP-1 in Cardiovascular Disease: Molecular Mechanisms and Clinical Implications." National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 22 Nov. 2014.
Wen-Rong Le et al, Cancer Res October 1,2014 74:3995.
Charo IF, Taubman MB. 2004. Chemokines in the pathogenesis of vascular disease. Circ Res 95:858–866.
Davies MH, Eubanks JP, Powers MR. 2006. Microglia and macrophages are increased in response to ischemia-induced retinopathy in the mouse retina. Mol Vis 12:467–477.
Spoettl T, Hausmann M, Herlyn M, Gunckel M, Dirmeier A, Falk W,Herfarth H, Schoelmerich J, Rogler G. 2006145:190–199.
Ip WK, Wong CK, Lam CW. 2006 Clin Exp Immunol 145:162–172. 21
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