Quantification of post-thaw viable CD34(+) cells better represents the actual composition of the graft and may be a more accurate predictor of haematopoietic engraftment than post-thaw total CD34(+) cell counts, or prefreeze determinations, especially for platelet engraftment. It is necessary to develop good quality controls for freezing and thawing procedures to minimize variance in cell viability.

Background We recently showed that PARP-1 may play a role in allergen (ovalbumin)-induced airway eosinophilia, potentially through a specific effect on IL-5 production. We also reported that while IL-5 replenishment promotes reversal of eosinophilia in lungs of PARP-1−/− mice, IL-4 or IgE replenishment do not, suggesting a potentially significant regulatory relationship between PARP-1 and IL-5. Objective To explore the mechanism by which PARP-1 regulates IL-5 production and to determine how PARP-1 inhibition blocks allergen-induced eosinophilia. Methods This study was conducted using a murine model of allergic airway inflammation and primary splenocytes. Results PARP-1 knockout-associated reduction in IL-5 upon allergen exposure occurs at the mRNA level. Such an effect appears to take place after IL-4 receptor activation as PARP-1 inhibition exerted no effect on JAK1/JAK3 activation. STAT-6 protein was severely downregulated in spleens of PARP-1−/− mice without any effect on mRNA levels, suggesting an effect on protein integrity rather than gene transcription. Interestingly, the degradation of STAT-6 in PARP-1−/− mice required allergen stimulation. Additionally, PARP-1 enzymatic activity appears to be required for STAT-6 integrity. The dowregulation of STAT-6 coincided with mRNA and protein reduction of GATA-3 and occupancy of its binding site on the IL-5 gene-promoter. IL-4 was sufficient to induce STAT-6 downregulation in both PARP-1−/− mice and isolated splenocytes. Such degradation may be mediated by calpain, but not by proteasomes. Conclusion These results demonstrate a novel function of PARP-1 in regulating IL-5 expression during allergen-induced inflammation and explain the underlying mechanism by which PARP-1 inhibition results in IL-5 reduction.

NF-kappaB may play a novel role in expression of IL-8 and COX-2 in H. pylori-induced gastric inflammation.

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