A Novel Anti-Inflammatory Function of Human Galectin-1: Inhibition of Hematopoietic Progenitor Cell Mobilization

Kiss, Judit; Kunstár, Aliz; Fajka-Boja, Roberta; Dudics, Valėria; Tóvári, József; Légrádi, Ádám; Monostori, Ėva; Uher, Ferenc

doi:10.1016/j.exphem.2006.09.015

« Previous Next »Experimental Hematology
Volume 35, Issue 2 , Pages 305-313, February 2007

A Novel Anti-Inflammatory Function of Human Galectin-1: Inhibition of Hematopoietic Progenitor Cell Mobilization

Judit Kiss
- Stem Cell Biology, National Medical Center, Budapest, Hungary
Aliz Kunstár
- Stem Cell Biology, National Medical Center, Budapest, Hungary
Roberta Fajka-Boja
- Lymphocyte Signal Transduction Laboratory, Institute of Genetics, Biological Research Center of Hungarian Academy of Sciences, Szeged, Hungary
Valėria Dudics
- Stem Cell Biology, National Medical Center, Budapest, Hungary
- Polyclinic of Hospitaller Brothers of St. John of God, Budapest, Hungary
József Tóvári
- Department of Tumor Progression, National Institute of Oncology, Budapest, Hungary
Ádám Légrádi
- Lymphocyte Signal Transduction Laboratory, Institute of Genetics, Biological Research Center of Hungarian Academy of Sciences, Szeged, Hungary
Ėva Monostori
- Lymphocyte Signal Transduction Laboratory, Institute of Genetics, Biological Research Center of Hungarian Academy of Sciences, Szeged, Hungary
Ferenc Uher
- Stem Cell Biology, National Medical Center, Budapest, Hungary
- Offprint requests to: Ferenc Uher, Ph.D., National Medical Center, Stem Cell Biology, Diószegi ut 64., Budapest, Hungary, H-1113

Received 7 June 2006; received in revised form 22 September 2006; accepted 25 September 2006.

Objective

The immunosuppressive and anti-inflammatory activity of mammalian galectin-1 (Gal-1) has been well established in experimental in vivo animal models and in vitro studies. Since the proliferation and migration of leukocytes represent a necessary and important step in response to the inflammatory insult, we have investigated whether Gal-1 affects the mobilization of hematopoietic progenitor cells (HPC) induced by cyclophosphamide (CY) and granulocyte colony-stimulating factor (G-CSF).

Methods

Bone marrow HPCs were mobilized with CY/G-CSF or CY/G-CSF plus human recombinant Gal-1 in BDF1 mice. Bone marrow (BM) and blood cells were taken at different time points and analyzed for their in vivo repopulating ability in lethally irradiated syngeneic animals. The number of myeloid progenitor cells in BM and blood samples was determined by colony-forming cell assay. Expression of surface markers (Sca-1, CD3ε, CD45R/B220, Ter-119, GR-1, and CD11b) on nucleated marrow cells was measured by flow cytometry. The lymphocytes, granulocytes, and monocytes in blood samples were counted after Giemsa staining.

Results

Gal-1 dramatically inhibited CY/G-CSF-induced HPC migration to the periphery as well as decreased peripheral neutrophilia and monocytosis in a dose- and time-dependent manner. In contrast, Gal-1 itself stimulated HPC expansion and accumulation within the BM. The presence of the lectin for inhibition of HPC mobilization was essential during the second half of the treatment. Moreover, Gal-1 inhbited transendothelial migration of BM-derived HPCs in response to SDF-1 in vitro.

Conclusion

Gal-1 blocked BM progenitor cell migration induced by CY/G-CSF treatment, indicating a novel anti-inflammatory function of the lectin. We suggest that the inhibition of HPC mobilization occurs mainly via obstructing the transendothelial migration of BM-derived cells including primitive hematopoietic and committed myeloid progenitor cells and mature granulocytes and monocytes.