What is chemokine?

Chemokine is a kind of small molecule basic protein. Its main function is to chemotactic cells to move in a direction. More than 50 chemokine have been found. With the deepening of research, the structure, function and in vivo role of chemokine and their receptors have been found by many researchers. The interaction of chemokine and their receptors can participate in many physiological functions, such as cell growth, development, differentiation, apoptosis and distribution, and also play an important role in pathological process, such as inflammatory reaction, pathogen infection, wound repair and tumor formation and metastasis.

Classification of chemokine

Chemokine generally consist of 70-125 amino acids with a molecular weight of 6-14 KD. According to the structure of the first-order peptide chain, the location and number of N-terminal cysteine residues can be divided into four subgroups: CC, CXC, C and C X3C (C is cysteine, X is arbitrary amino acid). The four types of chemokine have high similarity in structure and homology in amino acid sequence.According to the expression of chemokine and their role in the immune system, they can be divided into two categories: homeostasis chemokine and inflammatory chemokine. Chemokine of homeostasis are mainly expressed in homing sites, which have the function of maintaining homeostasis of the homeostasis of the homeostasis, and play a definite role in lymphocyte homing and maturation. Inflammatory chemokine are expressed by stimulated cells, such as the induction of inflammatory cytokines, bacterial toxins or other factors that destabilize the internal environment. Their main function is to recruit effector cells and play an important role in coordinating natural and acquired immune responses.

Most chemokine belongs to CC and CXC subgroups. There are 28 members of CC subgroup (CCL1-CCL28). They have strong chemotactic activity to neutrophils, monocytes, mast cells, dendritic cells, NK cells, T and B lymphocytes. The more important ones are monocyte chemotactic protein (MCP-1/CCL2), macrophage inflammatory protein (MIP/CCL3), (IP-10/CXCL10), stromal cell-derived factor-1 (SDF-1/CXCL12).The C subfamily contains two chemokine, XCL1 and XCL2, which are mainly expressed in thymus and act on CD8 + T lymphocytes. CX3C subfamily has only one chemokine CX3CL1, also known as fractalkine or neurotactin, which is the only membrane-bound chemokine, mainly acting on monocytes and neutrophils.

Chemokine receptor

Chemokine must bind to their receptors in order to play a biological role. Chemokine Receptor (Chemokine Receptor), a G protein-coupled receptor, has seven alpha-helical transmembrane regions rich in hydrophobic amino acids, which are mainly expressed in various leukocyte subsets derived from bone marrow, as well as in epithelial cells, vascular endothelial cells and nerve cells. Chemokine receptors can also be divided into four subfamilies according to their ligands: CCR, CXCR, XCR and CX3CR. Among them, 11 species (CCR1-CCR11) have been cloned, 6 species (CXCR1-CXCR6) have been cloned, and the other two subgroups have one species respectively: XCR 1 and CX3CR1.

Biological functions

Chemokine and their receptors have many biological functions. At first, chemokine and their receptors were found as chemokine. With the deepening of research, more and more chemokine and their receptors were found, such as in the development of immune cells and organs, immune response process, inflammatory response, pathogen infection, wound repair and tumorigenesis and metastasis play a wide range of physiological and pathological roles. Chemokine play a key role in bone marrow hematopoiesis. Studies have shown that at least 25 chemokine can regulate the proliferation of bone marrow progenitor cells. Mice lacking expression of CXCL12 and its specific receptor CX2CR4 have B lymphocyte dysgenesis and maturation and perinatal death.Thymus is an important organ for T lymphocyte development. There are many specific chemokine expressions, including CCL17, CCL19, CCL21, CCL25 and CXCL12. Chemokine and their receptors play a key role in the homing and colonization of lymphocytes to secondary lymphoid organs after maturation. Chemokine are also involved in the development and construction of secondary lymphoid organs. Chemokine control and regulate DC migration by acting on DCs with different chemokine receptor expression profiles. Chemokine participate in the inflammatory process by promoting the infiltration and activation of inflammatory cells in injured and infected tissues.

The relationship with disease

Chemokine and their receptors are closely related to human diseases, such as the expression of CCR3 and its ligands in the bronchial mucosa of asthmatic patients. Studies have shown that anti-CXCR1 and CXCR2 drugs contribute to the inflammatory response of chronic bronchitis, severe asthma and CCPD. Chemokine and their receptors play an important role in lymphocyte migration and recruitment in chronic hepatitis C. Many chemokine play an important role in tumor growth, invasion and metastasis through cell transformation, angiogenesis, protease secretion and organ specific metastasis.

In cancer and cancer research, it has been proved that many human cancers have complex chemokine networks, which may affect the degree and phenotype of leukocyte infiltration, angiogenesis, growth, survival and migration of cancer cells. Recent studies have found that the expression of specific chemokine is necessary for multiple tumors to metastasize. For example, CCR4 and CCR7 are highly expressed in human breast cancer cell lines and malignant breast tumors, while the ligands CX2CL12 and CCL21 of these receptors are highly expressed in organs with metastasis of cancer cells. The role of chemokine and their receptors in metastasis of other tumors has been reported, including melanoma, non-Hodgkin B-cell lymphoma, ovarian cancer, pancreatic cancer and so on. The production of CCL5 in breast cancer cells is associated with the progression of breast cancer, and only the expression of microchemokine is found in benign breast diseases. The expression level of CCL2 is also associated with the progression of breast cancer and the accumulation of macrophages.

Some related antibodies

1. Ulocuplumab

Recombinant human antibody to Human CXCR4.

2. PRO 140

Recombinant humanized (from mouse) antibody expressed in CHO binding to human CCR5. Anti-Human CCR5 Therapeutic Antibody is a humanized monoclonal antibody targeted against the CCR5 receptor found on T lymphocytes of the human immune system. It is being investigated as a potential therapy in the treatment of HIV infection.     

3. Mogamulizumab

Recombinant monoclonal antibody to CCR4. Mogamulizumab (USAN; trade name Poteligeo) is a humanized monoclonal antibody targeting CC chemokine receptor 4 (CCR4). It has been approved in Japan for the treatment of relapsed or refractory adult T-cell leukemia/lymphoma.