Granulocyte Colony-Stimulating Factor Attenuates Renal Ischemia-Reperfusion Injury by Inducing Myeloid-Derived Suppress… (2024)

Granulocyte Colony-Stimulating Factor Attenuates Renal Ischemia-Reperfusion Injury by Inducing Myeloid-Derived Suppress… (1) https://doi.org/10.1681/asn.2019060601

Видання: Journal of the American Society of Nephrology, 2020, №4, с.731-746

Видавець: Ovid Technologies (Wolters Kluwer Health)

Автори:

  1. Ji-Jing Yan
  2. Jung-Hwa Ryu
  3. Honglin Piao
  4. Ju Hee Hwang
  5. Dongkyu Han
  6. Sun-Kyung Lee
  7. Joon Young Jang
  8. Joongyub Lee
  9. Tai Yeon Koo
  10. Jaeseok Yang

Джерело фінансування: Ministry of Science

Анотація

<jats:sec> Significance Statement Myeloid-derived suppressor cells are innate suppressors that play an immunoregulatory role in autoimmunity, transplantation, and antitumor immunity; however, their effects on renal ischemia-reperfusion injury remain unclear. The authors showed that granulocyte colony-stimulating factor (G-CSF) increased renal infiltration of myeloid-derived suppressor cells after ischemia-reperfusion injury. When given before ischemia-reperfusion, G-CSF subsequently attenuated acute tissue injury, renal apoptosis, and renal inflammation; when given after ischemia-reperfusion, G-CSF facilitated renal recovery and attenuated renal fibrosis. They also showed that granulocytic myeloid-derived suppressor cells played a role in the beneficial effects induced by G-CSF <jats:italic toggle="yes">via arginase-1 and reactive oxygen species. These findings elucidate protective roles of G-CSF–induced myeloid-derived suppressor cells against ischemia-reperfusion injury and indicate that human studies investigating the therapeutic potential of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury are warranted. </jats:sec> <jats:sec> Background Granulocyte colony-stimulating factor (G-CSF) can increase populations of myeloid-derived suppressor cells, innate immune suppressors that play an immunoregulatory role in antitumor immunity. However, the roles of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury remain unclear. </jats:sec> <jats:sec> Methods We used mouse models of ischemia-reperfusion injury to investigate whether G-CSF can attenuate renal injury by increasing infiltration of myeloid-derived suppressor cells into kidney tissue. </jats:sec> <jats:sec> Results G-CSF treatment before ischemia-reperfusion injury subsequently attenuated acute renal dysfunction, tissue injury, and tubular apoptosis. Additionally, G-CSF treatment suppressed renal infiltration of macrophages and T cells as well as renal levels of IL-6, MCP-1, IL-12, TNF-<jats:italic toggle="yes">α, and IFN-<jats:italic toggle="yes">γ, but it increased levels of IL-10, arginase-1, and reactive oxygen species. Moreover, administering G-CSF after ischemia-reperfusion injury improved the recovery of renal function and attenuated renal fibrosis on day 28. G-CSF treatment increased renal infiltration of myeloid-derived suppressor cells (F4/80−CD11b+Gr-1int), especially the granulocytic myeloid-derived suppressor cell population (CD11b+Ly6GintLy6Clow); splenic F4/80−CD11b+Gr-1+ cells sorted from G-CSF–treated mice displayed higher levels of arginase-1, IL-10, and reactive oxygen species relative to those from control mice. Furthermore, these splenic cells effectively suppressed <jats:italic toggle="yes">in vitro T cell activation mainly through arginase-1 and reactive oxygen species, and their adoptive transfer attenuated renal injury. Combined treatment with anti–Gr-1 and G-CSF showed better renoprotective effects than G-CSF alone, whereas preferential depletion of myeloid-derived suppressor cells by pep-G3 or gemcitabine abrogated the beneficial effects of G-CSF against renal injury. </jats:sec> <jats:sec> Conclusions G-CSF induced renal myeloid-derived suppressor cells, thereby attenuating acute renal injury and chronic renal fibrosis after ischemia-reperfusion injury. These results suggest therapeutic potential of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury. </jats:sec>

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FAQs

How does granulocyte colony-stimulating factor work? ›

G-CSF stimulates the bone marrow to make more blood cells, and increases the number of some types of white blood cells in the blood. It can be used with, or after, chemotherapy. It can also be used before and after a stem cell transplant. G-CSF is made naturally in the body, but it can also be made as a drug.

What is ischemia reperfusion injury in the kidneys? ›

Ischemia is a condition in which the kidneys do not receive enough blood supply. Reperfusion is the restoration of blood flow after an ischemic event. Both of these processes can damage kidney cells and impair kidney function, resulting in AKI.

What is the drug name for granulocyte colony-stimulating factor? ›

There are different types of G-CSF, including: lenograstim (Granocyte) filgrastim (Neupogen, Zarzio, Nivestim) long acting (pegylated) filgrastim (pegfilgrastim, Neulasta, Pelmeg, Ziextenco) and lipegfilgrastim (Lonquex)

What is the prophylactic treatment of bone pain caused by granulocyte colony-stimulating factors? ›

For the prevention and treatment of bone pain occurring after or during GCSFs administration, acetaminophen and nonsteroidal anti-inflammatory agents are commonly used as first-line treatment; antihistamines, opioids and dose reduction of G-CSFs are considered as second line therapy.

How long does it take for G-CSF to work? ›

How long does it take G-CSF to work? It takes several days (about a week) for your bone marrow to make new cells with G-CSF. Most people taking G-CSF after chemotherapy continue taking it until their levels return to normal.

What is the most common side effect of G-CSF? ›

Results. Among 88 full-texts included, most studies were conducted during or shortly after G-CSF administration. Mild-to-moderate medullary bone pain was the most reported side effect, usually responsive to anti-inflammatory drugs although potentially impactful on daily functioning.

What are the symptoms of renal ischemia? ›

Symptoms
  • Extreme high blood pressure accompanied with clogged arteries in men over age 60.
  • High blood pressure that comes on immediately, particularly among young patients and females.
  • High blood pressure combined with vascular bruit (audible sound caused by choppy blood flow)

How do you treat ischemia reperfusion injury? ›

Treatment
  • Therapeutic hypothermia.
  • Hydrogen sulfide treatment.
  • Cyclosporin.
  • TRO40303.
  • Stem cell therapy.
  • Superoxide dismutase.
  • Metformin.
  • Riboflavin.

What are the symptoms of ischemia reperfusion injury? ›

With limb ischemia, pain that is out of proportion to the physical findings, decreased pulses, skin changes, and decreased sensations are all indicative of a possible reperfusion injury.

Is a G-CSF injection painful? ›

What to expect during your course of G-CSF injections. Every donor is different and will experience G-CSF injections differently, though the majority of donors will experience some side-effects, the most common being bone pain as your body is busy producing stem cells.

What are the side effects of filgrastim? ›

Possible Side Effects of Filgrastim (Table Version Date: June 16, 2023)
  • Nose bleed.
  • Anemia which may require blood transfusions.
  • Bruising, bleeding.
  • Diarrhea.
  • Bone pain.
  • Fever.
  • Tiredness.
  • Hair loss.

What are the anti inflammatory effects of granulocyte colony-stimulating factor? ›

G-CSF exerts a pivotal role in the control of the immune response and acts as an anti-inflammatory cytokine, preventing an overactivation of monocytes and lymphocytes by reducing the release of pro-inflammatory mediators while simultaneously activating the anti-inflammatory defense neutrophils [9].

How long does bone pain last with pegfilgrastim? ›

The duration of bone pain from Neulasta is usually 2 to 4 days.

Why do you get bone pain with filgrastim? ›

Filgrastim stimulates the bone marrow to produce many white blood cells, which can lead to pain in the bones. This pain is often felt in the bones of the thighs, hips, and upper arms.

How long does filgrastim take to work? ›

How long does it take for Filgrastim to work? It typically takes 1 to 3 weeks of administration for the white blood cells to come to normal levels.

What is the mechanism of action of colony stimulating factors? ›

Colony-stimulating factors (CSFs) are secreted glycoproteins that bind to receptor proteins on the surfaces of hematopoietic stem cells, thereby activating intracellular signaling pathways that can cause the cells to proliferate and differentiate into a specific kind of blood cell, usually white blood cells.

What is the mechanism of action of G-CSF? ›

G-CSFs act on hematopoietic cells by binding to specific cell surface receptors to stimulate the proliferation‚ differentiation‚ and maturation of neutrophil progenitors.

What is the mechanism of action of filgrastim? ›

Mechanism of Action

Filgrastim exhibits nonlinear pharmaco*kinetics with a short half-life of 3.5 hours, with filgrastim concentration and neutrophil count being the determinants of clearance. [16] The kidneys clear the drug. The bioavailability of filgrastim after subcutaneous administration is 60 to 70%.

How does G-CSF increase neutrophil production? ›

G-CSF acts by binding to its cognate cell surface receptor on target cells, causing the activation of intracellular signalling pathways mediating the proliferation, differentiation, function, and survival of cells in the neutrophil lineage.

References

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