Cell cycle activation of hematopoietic progenitor cells increases very late antigen-5-mediated adhesion to fibronectin

Objective. Recent studies suggested that trafficking of hematopoietic proge nitor cells is related to cell cycle status, We studied whether adhesion of progenitor cells to extracellular matrix proteins was modulated by cell cy cle transit, Materials and Methods. Mobilized peripheral blood CD34(+) cells were stimul ated ex vivo for 48 hours with stem cell factor, flt-3 ligand, and thrombop oietin and fractionated by adhesion to fibronectin or vascular cell adhesio n molecule-1 (VCAM-1). Adherent and nonadherent cells mere assayed for cell cycle status, long-term culture-initiating cell frequency, and integrin fu nction. Results, Binding to fibronectin, but not to VCAM-1, displayed a cell cycle selectivity as the adherent fraction to fibronectin was enriched in cycling CD34(+) cells and in cycling long-term culture-initiating cells compared t o the nonadherent fraction, Combined cell cycle and phenotypic analysis sho wed that the expression of VLA-5 was upregulated during S/G(2)+M but that o f VLA-4 remained constant, The selective binding of cycling CD34(+) cells t o fibronectin was reverted by anti-VLA-5 but not by anti-VLA-4 blocking ant ibodies. Also, cycling CD34(+) cells preferentially adhered to the VLA-5 bi nding domain but not to the VLA-4 binding domain of fibronectin, Adhesion o f cycling CD34(+) cells to fibronectin was a reversible process modulated b y cell cycle progression, because adherent cells could exit the cell cycle and return to a nonadhesive state within an additional 48-hour culture peri od. Conclusion. The results indicate that the enhanced binding capacity of ca c ling progenitor cells to fibronectin is mediated by VLA-5, (C) 2001 Interna tional Society for Experimental Hematology. Published by Elsevier Science I nc.