For example, it has been shown that sepsis is sometimes associate

For example, it has been shown that sepsis is sometimes associated with neutropenia,[36] accompanied by peripheral blood and BM myeloid progenitor cell mobilization and differentiation.[37] In the case of eosinophils, there Vismodegib research buy is a documented case of cryptococcal infection combined with sepsis, resulting in eosinophilia in a healthy individual.[38] Likewise, LPS has been shown to influence haematopoietic

dynamics through direct effects on progenitor cells, including rapid myeloid differentiation.[13] Increased Eo/B CFU production after LPS stimulation of CB CD34+ cells may represent a mechanism through which haematopoietic progenitor cells[15, 37] or their resulting mature progeny[39] can help to respond to invading bacterial species during acute infections. These mechanisms may also be operative in allergic (eosinophilic/basophilic) inflammation. Our data are interesting in the context find more of the type of immune response that can be generated in response to bacterial agents. Of note, IL-5 is an eosinophil-specific inducing cytokine,[40] whereas GM-CSF-responsive progenitors represent earlier stages of lineage commitment and therefore contribute to the development of several myeloid cells[37] including Eo/B cells, macrophages and

neutrophils. Therefore, the apparent skewing of the Eo/B progenitor population towards GM-CSF-responsive (Fig 1a), as opposed to IL-5-responsive, lineages (Fig 1b), with noted increases in GM CFU (data not shown), suggests that the progenitor response to LPS involves production of multi-cellular Progesterone (Eo/B[39] and GM[37]) inflammatory responses to pathogens or allergens. Although relatively high doses of LPS were used in the ex vivo culture system, this must be tempered by knowledge of the bio-availability of LPS in vivo. Physiologically, the fetus is exposed in vivo to LPS, because Gram-negative bacteria and associated LPS can be isolated from amniotic fluid in median concentrations of 0·05 μg/ml.[41] Though the minimal concentration of biologically

active LPS present within the intrauterine environment is unknown, soluble factors (e.g. sCD14) can modulate immune cell responses to LPS at 1000-fold lower concentrations than those observed in amniotic fluid.[42] The LPS concentration that we used in the current studies is in line with other in vitro progenitor cell studies,[12, 13] which have found minimal progenitor cell responses to LPS below 10 μg/ml. In addition, Roy et al.[43] have demonstrated that endotoxin levels range between 1 and 6 μg/g house dust in rural and urban homes. Hence, the dose of LPS used here appears to be in the physiological range of natural LPS exposure. We cannot conclude without addressing a couple of limitations of this study.

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