Mobilization of stem/progenitor cells by sulfated polysaccharides does not require selectin presence.
Employing carbohydrate ligands, which have been extensively used to block selectin function in vitro and in vivo, we have examined the involvement of such ligands in stem/progenitor cell mobilization in mice and monkeys. We found that sulfated fucans, branched and linear, are capable of increasing mature white cells in the periphery and mobilizing stem/progenitor cells of all classes (up to 32-fold) within a few hours posttreatment in a dose-dependent manner. To elicit the effect, the presence of sulfate groups was necessary, yet not sufficient, as certain sulfated hexosamines tested (chondroitin sulfates A or B) were ineffective. Significant mobilization of stem/progenitor cells and leukocytosis was elicited in selectin-deficient mice (L(-/-), PE(-/-), or LPE(-/-)) similar to that of wild-type controls, suggesting that the mode of action of sulfated fucans is not through blockade of known selectins. Other mechanisms have been entertained, in particular, the release of chemokines/cytokines, including some previously implicated in mobilization. Significant increases were documented in the levels of seven circulating chemokines/cytokines within a few hours after fucan sulfate treatment and support such a proposition. Additionally, an increase was noted in plasma metalloproteinase (MMP) 9, which might independently contribute to the mobilization process by enzymatically facilitating chemokine/cytokine release. Mobilization by sulfated polysaccharides provides a distinct paradigm in the mobilization process and uncovers an additional novel in vivo biological role for sulfated glycans. As similarly sulfated compounds were ineffective in vivo, the data also underscore the fact that polysaccharides with similar structures may elicit diverse in vivo effects.
Sweeney
E A
EA
Department of Medicine, Division of Hematology, University of Washington, Seattle, WA 98195-7710, USA.
Priestley
G V
GV
Nakamoto
B
B
Collins
R G
RG
Beaudet
A L
AL
Papayannopoulou
T
T
D000818:Animals; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D019650:Hematopoietic Stem Cell Mobilization; D008254:Macaca nemestrina; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D011134:Polysaccharides / Q000494:pharmacology*; D019087:Selectins / Q000502:physiology*; D013329:Structure-Activity Relationship
D018925:Chemokines; D016207:Cytokines; D011134:Polysaccharides; D019087:Selectins; C007789:fucoidan; D020780:Matrix Metalloproteinase 9