GRANZYME-B AND PERFORIN LYTIC PROTEINS ARE EXPRESSED IN CD34(+) PERIPHERAL-BLOOD PROGENITOR CELLS MOBILIZED BY CHEMOTHERAPY AND GRANULOCYTE-COLONY-STIMULATING FACTOR

Granzyme B and perforin are cytoplasmic granule-associated proteins used by cytotoxic T lymphocytes and natural killer (NK) cells to kill their targets. However, granzyme B gene expression has also been detected in a non-cytotoxic hematopoietic murine multipotent stem cell line, FDCP-Mix. The objective of the present study was to investigate whether granzyme B and perforin could be expressed in human hematopoietic CD34(+) cells and if present, discover what their physiologic relevance could be. The primitive CD34(+) human cell line KG1a was investigated first and was found to express granzyme B and perforin. Highly purified hematopoietic stem/progenitor cells were then selected using the CD34 surface antigen as marker. Steady-state bone marrow (BM) CD34(+) cells did not contain these proteins, Peripheral blood (PB) CD34(+) cells, which had been induced to circulate, were also analyzed. After chemotherapy (CT) and granulocyte colony-stimulating factor (G-CSF) treatment, CD34(+) cells strongly expressed mRNAs and proteins of granzyme B and perforin, In contrast, CD34(+) cells mobilized by G-CSF alone were negative. Western blot analysis further showed that granzyme B and perforin proteins were identical in CD34(+) cells and activated PBLs, Such proteins might be implicated in the highly efficient migration of CD34(+) stem/progenitor cells from BM to PB after CT and G-CSF treatment. The cellular adhesion mechanisms involved in the BM homing of CD34(+) cells are disrupted at least temporarily after CT. The Asp-ase proteolytic activity of granzyme B on extracellular matrix proteins could be used by progenitor cells for their rapid detachment from BM stromal cells and perforin might facilitate their migration across the endothelial cell barrier. (C) 1995 by The American Society of Hematology.