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Expression and function of adhesion molecules on human hematopoietic stem
cells: CD34+ LFA-1- cells are more primitive than CD34+ LFA-1+ cells
Y Gunji, M Nakamura, T Hagiwara, K Hayakawa, H Matsushita, H Osawa, K Nagayoshi, H Nakauchi, M Yanagisawa and Y Miura
Department of Pediatrics, Jichi Medical School, Tochigi-ken, Japan.
Advances in fluorescence-activated cell sorter technology have brought
about multicolor analysis of cell phenotypes. To clarify the phenotypes of
human hematopoietic stem cells (HSCs), we initially prepared novel
antibodies against CD34 and labeled one of them (4A1) with allophycocyanin
(APC). With this, we analyzed the phenotypes of CD34+ HSCs and showed that
primitive HSCs or CD34+CD33- cells expressed adhesion molecules such as
CD43, CD44, CD11a, CD11c, CD18, and leukocyte adhesion molecule (LAM-1).
The more primitive hematopoietic cells or CD34+CD38- cells also expressed
CD11a and CD18 with an incidence of 20% to 30%. To clarify the role of
adhesion molecules in HSCs, we examined the colony forming capacity after
long-term culture with allogeneic irradiated stromal layers. Among
CD34+CD33- cells, CD18+ cells gave rise to colony-forming cells (CFCs) on
stromal layers, but reached a maximum at week 2, after which the number of
generated CFCs decreased. On the other hand, CD18- cells generated less
CFCs than CD18+ cells at 2 to 3 weeks, but increased after 4 weeks of
culture. When CD18 or CD11a antibody was added to a coculture system of
CD34+CD33- cells with stromal layers, the number of generated CFCs
decreased significantly compared with the no antibody control. Leukocyte
function-associated antigen-1 (LFA-1) (CD11a/CD18) was expressed on some
populations of hematopoietic cells and contributed to the proliferation by
interacting with stromal cells. However, more primitive cells capable of
reconstituting hematopoiesis did not express LFA-1. These data provide a
rationale for the administration of anti- LFA-1 antibody after bone marrow
transplantation for reducing the graft failure.
Volume 80,
Issue 2,
pp. 429-436,
07/15/1992
Copyright © 1992 by The American Society of Hematology
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