What Factors Affect Cytokine Production?

Stem cell factor is also called mast cell growth factor (MGF), Kit ligand (KL) and Steel factor (SLF). It is an acidic glycoprotein produced by stromal cells in the bone marrow microenvironment. The glycosyl group is connected to the N and O groups of the peptide bond, and has a relative molecular mass of 31 000 to 36 000. It is composed of two non-covalently bonded identical subunits. Isoelectric point PI = 3.8. SCF has a total of 273 amino acids. From -25 to -1 are signal peptides, +1 to +189 are extramembrane functional regions, +190 to +216 are transmembrane regions, and +217 to +248 are cytoplasmic functional regions. Mouse and human SCF have 83% homology.

Stem cell factor

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SCF is encoded in mice by the Steel site on chromosome 10. The person is located at 12 q22 24. SCF exists in two forms: soluble and membrane-bound.

In humans, mRNA encoding 248 amino acids (SCF248) has a protein cleavage site in its sixth exon. Thus mRNA expresses a soluble SCF of 165 amino acids. It encodes 220 amino acid mRNA (SCF220), and there is no protein cleavage site in the sixth exon. This mRNA expresses membrane-bound SCF. In mice, soluble SCF can be cut by SCF248 at exon 6 or SCF248 and SCF220 by exon 7. Membrane-bound SCF is expressed by SCF220.

Both forms of SCF are biologically active. Mouse and human SCF have almost equal biological activity on artificial blood cells, but on mouse cells, mouse SCF has a 800-fold stronger biological effect than human SCF.

SCF, along with other cytokines, induces stem and progenitor cell proliferation, prolongs their survival, and causes stem and progenitor cell mobilization. Although the receptors of SCF are not significantly different in progenitor cells, SCF induces erythroid progenitor cells to proliferate more strongly than granulocytes-single progenitor cells, which may be other specific factors affecting the progenitor cell response to SCF. Applying SCF and granulocytes to mice

Low serum SCF has been used as a cause of hematopoietic dysfunction. Serum SCF levels have been reported to be low in patients with aplastic anemia, myelodysplastic syndrome, and bone marrow transplantation. Abkowitz et al. Tested the serum SCF of 34 patients with pure red aplastic anemia compared with normal people, which was not statistically significant. It is believed that serum SCF levels may not be clinically related. However, serum SCF is soluble SCF, and membrane-bound SCF cannot be detected.

Weaver and other 48 patients with epithelial ovarian cancer were given 3 g · (m2) -1 cyclophosphamide infusion on the first day. The infusion was completed in 4 hours, and mesna 6 g · (m2) -1 was infused for 12 hours. Then 48 cases were randomly divided into 4 groups, each person was injected with 5 g · kg · d-1G-CSF, and 9 cases in each group were treated with recombinant human SCF. Each group was given 5 g · kg-1.d-1, 10 g · kg-1.d-1, 15 g · kg-1.d-1, and 20 g · kg-1.d-1. The application was started 48 hours after chemotherapy until the peripheral blood WBC was 4.0 × 109 L-1. At this time, peripheral blood single component collection was performed. The results showed that long-term culture starting cells (LTC-IC) in the SCF 20 g · kg-1.d-1 group increased by 5.8 times, CD34 + cells increased by 3 times, and CD34 + CD33- cells increased by 64 times compared to the G-CSF group alone. . Glaspy et al randomized 215 patients with high-risk breast cancer after chemotherapy, using G-CSF 10 mg · kg-1.d-1 alone for 7 days, G-CSF 10 g · kg-1.d-1 and recombinant human SCF 5,10,15,20,25,30 g · kg-1.d-1 combined for 7,10,13 days. Peripheral blood leukocyte single component collection was performed on the last 3 days of each therapy. As a result, peripheral blood was started on the 5th day after applying 20 g · kg-1.d-1SCF and 10 g · kg-1.d-1G-CSF. Apheresis is the most appropriate dose and best solution for mobilizing peripheral blood progenitor cells. Begley et al. Randomized 62 patients with early breast cancer before chemotherapy to receive 12 g · kg-1.d-1G-CSF and the same dose of G-CSF plus rhSCF 5, 10, 15 g · kg-1.d-1 for 7 days And 10 g · kg-1.d-1SCF for 10 d and G-CSF was added for 7 d on the fourth day. It was found that the peripheral blood hematopoietic progenitor cells increased more significantly after pretreatment with SCF 3 d and then with the combined treatment group. SCF is usually injected subcutaneously. The most common side effects were mild edema of the skin and redness and swelling outside the area. It usually starts 4 hours after injection and lasts for 24 to 48 hours, and then returns to normal. Occasionally allergic reactions are reported, anti-allergic prevention can be given before application.

Although the research on stem cell factors has been deepened, there are still unresolved problems. (1) The specific mechanism by which SCF interacts with its receptor c-kit to trigger intracellular changes remains to be elucidated; (2) SCF has more basic research, is not widely used in clinical applications, and the effect on aplastic anemia is uncertain; SCF can guide vector transfection in vitro, and there is no evidence in vivo.