Difference between revisions of "Part:BBa K1993012"

Revision as of 16:30, 20 October 2020

CCR2

Chemokine receptors are receptors found on the surface of certain cells that interact with chemokines. They have a 7-transmembrane (7-TM) structure and couple to G-protein for signal transduction within a cell. [1] (Figure 1) Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux intracellular calcium (Ca2+) ions, initiate chemotaxis and guide the cell to a desired location. (Figure 2)

Figure 1. typical structure of a chemokine receptor.

Figure 2. the mechanism of interaction between a chemokine and a chemokine receptor.

Under the circumstances of inflammation, various kinds of cytokines, including chemokines, are released by the lesions. Guided by the chemokines, cells expressing chemokine receptors move towards the lesions where they can function better.[2] What’s more, different diseases would release different pools of chemokines, which would recruit different effector cells. See our disease table-chemokine

Based on the chemotaxis theory, in order to enhance the homing ability of our marvelous mesenchymal stem cells (MSCs) due to lack of enough chemokine receptors on their cell surface, we, SYSU-MEDICINE, had constructed a series of chemokine receptors that corresponding to different inflammatory diseases as far as possible. Among which, CCL2 is a significant chemokine (CCR2 is its chemokine receptor) in Cardiovascular disease(CVD) and Experimental Allergic Encephalomyelitis(EAE) . See our disease table-chemokine

We acquired this gene from peripheral mononuclear blood cells (PMBCs) and purified it. (Figure 3) Then we constructed it under the control of EF-1α by Gateway technology. (Figure 4)

Figure 3 Purification of CCR2

Figure 4 EF-1α- CCR2

Then, we tested the chemotaxis of engineered MSCs by conducting Transwell assay against CCL2. To our excitement, our engineered MSCs had improved their homing ability with chemokine receptor CCR2(Figure 5).

Figure 5. Transwell Assay of CCR2.

MIT MAHE 2020

Summary

CCR2, a G protein-coupled receptor, is the key functional receptor for CCL2. The activation of the ligand-receptor binding leads to the activation of intracellular signaling cascades that mediate chemotactic response. CCR2 has both pro-inflammatory (mediated by APC and T cells) and anti-inflammatory (mediated by regulatory T cells) effects.

References

[1]Allen, Samantha J.; Crown, Susan E.; Handel, Tracy M. (2007-01-01). "Chemokine: receptor structure, interactions, and antagonism". Annual Review of Immunology. 25: 787–820.

[2] Griffith J W, Sokol C L, Luster A D. Chemokines and chemokine receptors: positioning cells for host defense and immunity.[J]. Annual Review of Immunology, 2014, 32(1):659-702.

[3] Boring L, Gosling J, Cleary M, Charo IF. Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis. Nature. 1998; 394: 894– 7. Crossref CAS PubMed Web of Science®Google Scholar

[4] Quinones MP, Ahuja SK, Jimenez F, Schaefer J, Garavito E, Rao A, et al. Experimental arthritis in CC chemokine receptor 2‐null mice closely mimics severe human rheumatoid arthritis. J Clin Invest. 2004; 113: 856– 66. Crossref CAS PubMed Web of Science®Google Scholar

[5] Martin AP, Rankin S, Pitchford S, Charo IF, Furtado GC, Lira SA. Increased expression of CCL2 in insulin‐producing cells of transgenic mice promotes mobilization of myeloid cells from the bone marrow, marked insulitis, and diabetes. Diabetes. 2008; 57: 3025– 33. Crossref CAS PubMed Web of Science®Google Scholar

[6] Kang YS, Cha JJ, Hyun YY, Cha DR. Novel C‐C chemokine receptor 2 antagonists in metabolic disease: a review of recent developments. Expert Opin Investig Drugs. 2011; 20: 745– 56.

Sequence and Features