Effect of leukotactin-1 on the protection in vivo of myeloid progenitor cells against cytotoxic chemotherapeutics.
Leukotactin-1 (Lkn-1) is a human CC chemokine that induces chemotaxis of neutrophils, monocytes, eosinophils, and lymphocytes and suppresses colony formation of myeloid progenitor cells in vitro. Present studies evaluated the myeloprotective capabilities of Lkn-1 in vivo against Ara-C and 5-fluorouracil (5-FU). The effect of Lkn-1 on myelopoiesis was first assessed in vivo by injecting recombinant Lkn-1 in C3H/HeJ mice. Lkn-1 rapidly decreased cycling rates and absolute numbers of myeloid progenitor cells in marrow. Lkn-1 administration prior to and during the chemotherapeutics treatment resulted in increased progenitors for colony-forming units-granulocyte/macrophage (CFU-GM), colony-forming units-granulocyte/erythroid/megakaryocyte/macrophage (CFU-GEMM), and burst-forming units-erythroid (BFU-E) compared with a saline-treated group. The protective effects lasted until day 3 after the termination of Ara-C administration and until day 7 after the termination of 5-FU administration. The results indicate that Lkn-1 protects bone marrow myeloid progenitor cells when cytotoxic chemotherapeutics are used in a preclinical setting. These results may be of use in clinical treatment for myeloprotection.
Kim
Won Y
WY
The Immunomodulation Research Center and Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea.
Broxmeyer
Hal E
HE
Han
In-Seob
IS
Park
Doo H
DH
Lee
Ki-Man
KM
Vinay
Dass S
DS
Kwon
Byoung S
BS
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000494:pharmacology* / Q000502:physiology*; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000627:therapeutic use; D004247:DNA / Q000378:metabolism; D005472:Fluorouracil / Q000627:therapeutic use; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008957:Models, Genetic; D023461:Myeloid Progenitor Cells / Q000187:drug effects / Q000276:immunology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D054407:Chemokine CCL4; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D011994:Recombinant Proteins; D003561:Cytarabine; D004247:DNA; D005472:Fluorouracil