Pathogenesis of chronic graft-versus-host disease (cGVHD) is largely unknown. It is important to determine the responsible cell types and the factors that play roles to recruit these cells into sites of disease. We examined whether monocytes and chemokine fractalkine/receptor CX3CR1 axis might be involved. We found that the absolute number of CX3CR1+ monocytes in the blood was significantly decreased in patients with severe cGVHD. Immunohistochemical staining revealed the extensive infiltration of CD14+ cells as well as strong expression of fractalkine in the cGVHD skin. The number of infiltrated CD14+ cells on the margin of fractalkine+ epidermis was larger in cGVHD skin compared to that of acute graft-versus-host disease, whereas no difference was observed in CD3+ T cells. These results suggest that CX3CR1+ monocytes may be recruited from the circulation to the fractalkine+ epidermis in cGVHD, and highlight these cells and this chemokine/receptor axis as additional targets for cGVHD therapy.

Dock2 has been shown to be indispensable for chemotaxis of mature lymphocytes as a critical Rac activator. However, the functional expression of Dock2 in immature hematopoietic cells is unclear. In this study, we demonstrate that Dock2 is broadly expressed in bone marrow (BM) hematopoietic compartment, including hematopoietic stem/progenitor cell (HSC/HPC) fraction. Response of Dock2-/- HPCs to CXCL12 in chemotaxis and actin polymerization in vitro was impaired, although alpha4 integrin activation by CXCL12 was not altered. Myelosuppressive stress on HSCs in vivo, such as consecutive 5-FU administration and serial bone marrow transplantation, did not show hematopoietic defect in Dock2-/- mice. Long-term engraftment of transplanted Dock2-/- BM cells was severely impaired in competitive reconstitution. However, this was not intrinsic to HSCs but originated from the defective competition of Dock2-/- lymphoid precursors. These results suggest that Dock2 plays a significant role in BM lymphopoiesis, but is dispensable for HSC engraftment and self-renewal.

Background Delayed syncopal‐type complications are infrequent among blood donors, but sometimes have critical consequences, such as severe injury. We retrospectively investigated the characteristics of donors with delayed syncopal‐type complications or falls. Study design and methods We defined a delayed reaction (DR) as syncopal‐type complications occurring >20 min after needle removal. Subjects were stratified by sex, age, estimated blood volume (EBV), body mass index (BMI) and frequency of donation. Multiple logistic regression analysis and propensity score weighted M estimation were performed to evaluate the covariate‐adjusted risk of syncopal DRs among donors giving 400 ml of whole blood (WB). The DR rate was calculated as the number of DRs divided by the number of all syncopal‐type reactions after needle removal. The risk of falls was assessed similarly. Donors who discontinued before completing phlebotomy (donation of 400 ml) were excluded. Results Among 3818 syncopal‐type reactions after needle removal, there were 359 DRs and 93 falls. Elderly donors and female donors with syncopal‐type reactions had a significantly higher risk of DRs (P for trend < 0·001). Elderly donors with syncopal‐type reactions also had a higher risk of falls (P for trend < 0·001). Among all donors with syncopal‐type reactions, the risk of DRs or falls was not correlated with EBV, BMI or donation frequency. Conclusion In female donors and elderly donors (donating 400 ml of WB), syncopal‐type reactions tended to be delayed. Elderly donors with syncopal‐type reactions had a significantly higher risk of falls.

Background and Objectives To evaluate the possible effects of environmental surroundings on blood donor reactions, we analysed vasovagal reaction rates before and after renovation of the Yurakucho Blood Donation Center in Tokyo. Materials and MethodsWe conducted a retrospective cohort study based on data stored in a computerized database. The vasovagal reaction rates associated with blood donation during two separate 3-year periods were compared, that is prior to (October 2007 to September 2010) and after (October 2010 to September 2013) the renovation of the Yurakucho Blood Donation Center. The renovation included the following interventions: (1) expansion of the phlebotomy area from 188Á0 to 322Á4 m 2 to accommodate 22 beds; (2) expansion of the reception/lounge area from 155Á2 to 267Á1 m 2 with modification for a more relaxed atmosphere; and 3) addition of well-controlled air conditioning. ResultsThe total reaction rate decreased from 0Á65% (1302 reactions/200 181 donations) to 0Á32% (606 reactions/191 966 donations) before and after the renovation, respectively, representing a 51% reduction (P < 0Á001). During the pre-intervention period, reaction rates in winter were higher than those in other seasons, and the reaction rate was correlated with room temperature. It was also suggested that environmental factors other than room temperature might play an important role. Multivariate logistic regression analysis of risk factors demonstrated that the male gender was the strongest favourable factor and young age was the next to strongest favourable factor. ConclusionOur results suggest that providing a comfortable environment for blood donation may lead to fewer vasovagal reactions.

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