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Granulocyte-colony stimulating factor increases CD123hi blood dendritic cells with altered CD62L and CCR7 expression
Slavica Vuckovic1, Min Kim, Dailal Khalil
1Mater Medical Research Institute, South Brisbane, Queensland, Australia.
Insights
Granulocyte-colony stimulating factor (G-CSF) mobilization for peripheral blood stem cell (PBSC) collection alters blood dendritic cell (BDC) counts. G-CSF impacts BDC subsets and homing molecules, potentially affecting immune cell distribution post-apheresis.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Peripheral blood stem cell (PBSC) mobilization is crucial for hematopoietic stem cell transplantation.
- Granulocyte-colony stimulating factor (G-CSF) is a key agent used in PBSC mobilization protocols.
- Blood dendritic cells (BDCs) play a vital role in immune regulation and are potential targets during mobilization.
Purpose of the Study:
- To investigate the impact of G-CSF-containing PBSC mobilization on BDC subsets (CD123(hi)BDC and CD11c(+)BDC) in healthy donors and patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL).
- To analyze changes in the expression of homing molecules (CD62L, CCR7, CD49d) on BDCs following PBSC mobilization.
- To understand how G-CSF mobilization affects BDC counts and their potential homing capabilities.
Main Methods:
- Analysis of BDC subsets (CD123(hi)BDC and CD11c(+)BDC) and expression of CD62L, CCR7, and CD49d in healthy donors, MM, and NHL patients.
- Comparison of BDC counts and marker expression before and after G-CSF administration and PBSC apheresis.
- Utilized flow cytometry to quantify cell populations and surface marker expression.
Main Results:
- G-CSF mobilization significantly altered BDC counts: CD123(hi)BDC increased in healthy donors and MM patients, while CD11c(+)BDC decreased in NHL patients.
- Post-apheresis, elevated CD123(hi)BDC counts persisted, and low CD11c(+)BDC counts showed a trend toward recovery within 2-5 days.
- Down-regulation of CD62L and up-regulation of CCR7 were observed on CD123(hi)BDCs in most healthy donors and MM patients, suggesting altered homing potential.
Conclusions:
- PBSC mobilization protocols using G-CSF can dynamically alter the counts of distinct blood dendritic cell subsets.
- Changes in BDC counts and expression of homing molecules like CD62L and CCR7 may influence the distribution of these cells between blood and tissues.
- These findings highlight the immunomodulatory effects of G-CSF mobilization and its potential impact on immune cell trafficking.
Abstract:
Changes in blood dendritic cell (BDC) counts (CD123(hi)BDC and CD11c(+)BDC) and expression of CD62L, CCR7, and CD49d were analyzed in healthy donors, multiple myeloma (MM), and non-Hodgkin lymphoma (NHL) patients, who received granulocyte-colony stimulating factor (G-CSF) containing peripheral blood stem cell (PBSC) mobilization protocols. Low-dose G-CSF in healthy donors (8-10 microg/kg/d subcutaneously) and high-dose G-CSF in patients (30 microg/kg/d) increased CD123(hi)BDC (2- to 22-fold, mean 3.7 x 10(6)/L-17.7 x 10(6)/L and 1.9 x 10(6)/L-12.0 x 10(6)/L) in healthy donors and MM but decreased CD11c(+)BDC (2- to 10-fold, mean 5.7 x 10(6)/L-1.6 x 10(6)/L) in NHL patients, on the day of apheresis, compared with steady state. After apheresis, CD123(hi)BDC counts remained high, whereas low CD11c(+)BDC counts tended to recover in the following 2-5 days. Down-regulation of CD62L and up-regulation of CCR7 on CD123(hi)BDC were found in most healthy donors and MM patients. CD49d expression was unchanged. Thus, PBSC mobilization may change BDC counts by altering molecules necessary for BDC homing from blood into tissues.