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Blood, 15 December 2000, Vol. 96, No. 13, pp. 4194-4203
HEMATOPOIESIS
Characterization and functional analysis of laminin
isoforms in human bone marrow
Ulrich Siler,
Martina Seiffert,
Sabine Puch,
Allan Richards,
Beverly Torok-Storb,
Claudia A. Müller,
Lydia Sorokin, and
Gerd Klein
From the University Medical Clinic, Section for
Transplantation Immunology and Immunohematology, Tübingen,
Germany; Department of Pathology, University of Cambridge, Cambridge,
England; Transplantation Biology, Clinical Research Division, Fred
Hutchinson Cancer Research Center, Seattle, WA; and Nikolaus Fiebinger
Center for Molecular Medicine, University of Erlangen-Nuremberg,
Germany.
Laminins are a family of disulfide-linked heterotrimeric proteins
consisting of 3 different subunits termed  ,  , and  chains. Combinations of 11 characterized laminin subunits (1-5,
1-3, and 1-3) generate at least 12 laminin isoforms, which
can serve different functions. Although expression of laminin in the
hematopoietic microenvironment has been known for many years, the
nature of the laminin isoforms present in the human bone marrow is
poorly characterized. The present study attempts to clarify this issue. Reverse transcriptase-polymerase chain reaction analysis of human bone
marrow stromal cells suggested the expression of many laminin isoforms
in the marrow. Northern blot and immunoblot analysis, however, showed
that laminin-8/9 and laminin-10/11 are the most abundant laminin
isoforms synthesized by human bone marrow stromal cells. Other
isoforms, if present, certainly play a minor role in the hematopoietic
microenvironment. Functionally, laminin-10/11 preparations showed
strong adhesive interactions with human CD34+ cell lines.
Antibodies against the 1 integrin subunit inhibited these
interactions. Other laminin isoforms, especially laminin-1 and
laminin-2/4, showed only weak or no adhesive interactions with the
hematopoietic cell lines tested, explaining former negative results. In
addition to its adhesion-mediating properties, laminin-10/11 preparations also showed a mitogenic activity for human hematopoietic progenitor cells. Taken together, these data suggest that laminin in
the bone marrow plays a hitherto unexpected important function in the
development of hematopoietic progenitor cells.
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