Mobilization of stem/progenitor cells by sulfated polysaccharides does notrequire selectin presence

Employing carbohydrate ligands, which have been extensively used to block s electin function in vitro and in vivo, we have examined the involvement of such ligands in stem/progenitor cell mobilization in mice and monkeys. We f ound that sulfated fucans, branched and linear, are capable of increasing m ature 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-depe ndent manner. To elicit the effect, the presence of sulfate groups was nece ssary, yet not sufficient, as certain sulfated hexosamines tested (chondroi tin sulfates A or B) were ineffective. Significant mobilization of stem/pro genitor 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 sel ectins. Other mechanisms have been entertained, in particular, the release of chemokines/cytokines, including some previously implicated in mobilizati on, Significant increases were documented in the levels of seven circulatin g 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 mobi lization process by enzymatically facilitating chemokine/ cytokine release. Mobilization by sulfated polysaccharides provides a distinct paradigm in t he mobilization process and uncovers an additional novel in vivo biological role for sulfated glycans. As similarly sulfated compounds were ineffectiv e in vivo, the data also underscore the fact that polysaccharides with simi lar structures may elicit diverse in vivo effects.