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

Granzyme B and perforin are cytoplasmic granule-associated proteins us ed by cytotoxic T lymphocytes and natural killer (NK) cells to kill th eir targets. However, granzyme B gene expression has also been detecte d in a non-cytotoxic hematopoietic murine multipotent stem cell line, FDCP-Mix. The objective of the present study was to investigate whethe r granzyme B and perforin could be expressed in human hematopoietic CD 34(+) 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 purifie d hematopoietic stem/progenitor cells were then selected using the CD3 4 surface antigen as marker. Steady-state bone marrow (BM) CD34(+) cel ls did not contain these proteins, Peripheral blood (PB) CD34(+) cells , which had been induced to circulate, were also analyzed. After chemo therapy (CT) and granulocyte colony-stimulating factor (G-CSF) treatme nt, 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 pe rforin proteins were identical in CD34(+) cells and activated PBLs, Su ch proteins might be implicated in the highly efficient migration of C D34(+) stem/progenitor cells from BM to PB after CT and G-CSF treatmen t. The cellular adhesion mechanisms involved in the BM homing of CD34( +) cells are disrupted at least temporarily after CT. The Asp-ase prot eolytic 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 endoth elial cell barrier. (C) 1995 by The American Society of Hematology.