[Protection of hematopoietic stem cells by MIP-1alpha and PF4 against the cytotoxicity of chemotherapeutic agents].
OBJECTIVE
To study the protective effects of macrophage inflammatory protein-1alpha (MIP-1alpha) and platelet factor 4 (PF4), alone and in combination, on hematopoietic stem/progenitor cells against the cytotoxicity of chemotherapeutic drugs.


METHODS
Bone marrow and cord blood mononuclear cells (BMMNC and CBMNC) and HL-60 cells were pretreated with MIP-1alpha, PF4, MIP-1alpha + PF4, and PBS respectively for 48 hours, and then incubated with DNR for an additional 24 hours. Cell viability, cell cycle, CD(34)(+) CD(38)(-) cells, colony forming units (CFU) and protein expression of p16, p27 gene were measured.


RESULTS
(1) Cell viability, the number of CD(34)(+) CD(38)(-) cells and CFU yields of BMMNC and CBMNC in MIP-1alpha and PF4 groups were significantly higher than that in control groups (P < 0.05). (2) Cells in S + G(2) phase in MIP-1alpha and PF4 groups were significantly fewer than that in control groups (P < 0.05). (3) MIP-1alpha upregulated the expression of p16 gene of stem/progenitor cells. PF4 showed no effects on expression of both p16 and p27 genes. (4) Hematopoietic protection of MIP-1alpha was stronger than that of PF4. No cooperative effect could be seen in combination of the two agents. (5) Cell viability, cell cycle and expression of p16 and p27 gene of HL-60 cells were not affected by either MIP-1alpha or PF4.


CONCLUSIONS
MIP-1alpha and PF4 can reversibly and selectively protect hematopoietic stem/progenitor cells against cytotoxicity of chemotherapeutic agents. MIP-1alpha can suppress cell proliferation by upregulating the expression of p16 gene and block the cell cycle at G(0) phase, resulting in the elevation of cell resistance to chemotherapeutic drugs.
Huang
K
K
Pediatric Department, Sun Yat-sen Memorial Hospital of Zhongshan Medical University, Guangzhou 510120, China.
Huang
S
S
Pan
J
J
Wu
Y
Y
D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003114:Colony-Forming Units Assay; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003630:Daunorubicin / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D018922:HL-60 Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D010978:Platelet Factor 4 / Q000494:pharmacology*; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000032:analysis
D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D018952:Antigens, CD34; D018797:Cell Cycle Proteins; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010978:Platelet Factor 4; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D003630:Daunorubicin