Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis.

Tissue macrophages comprise a heterogeneous group of cell types differing in location, surface markers and function. Red pulp macrophages are a distinct splenic subset involved in removing senescent red blood cells. Transcription factors such as PU.1 (also known as Sfpi1) and C/EBPalpha (Cebpa) have general roles in myelomonocytic development, but the transcriptional basis for producing tissue macrophage subsets remains unknown. Here we show that Spi-C (encoded by Spic), a PU.1-related transcription factor, selectively controls the development of red pulp macrophages. Spi-C is highly expressed in red pulp macrophages, but not monocytes, dendritic cells or other tissue macrophages. Spic(-/-) mice have a cell-autonomous defect in the development of red pulp macrophages that is corrected by retroviral Spi-C expression in bone marrow cells, but have normal monocyte and other macrophage subsets. Red pulp macrophages highly express genes involved in capturing circulating haemoglobin and in iron regulation. Spic(-/-) mice show normal trapping of red blood cells in the spleen, but fail to phagocytose these red blood cells efficiently, and develop an iron overload localized selectively to splenic red pulp. Thus, Spi-C controls development of red pulp macrophages required for red blood cell recycling and iron homeostasis.

Leukocytosis as a predictor of severe injury in blunt trauma.

OBJECTIVE: The objective of this study was to determine if the white blood cell count can predict severity of injury in blunt trauma victims. METHODS: This was a retrospective study comparing two groups of blunt trauma victims by severity of injury, one with significant injury and one without significant injury, and comparing their initial WBC in the emergency department (ED). We also examined if WBC correlates with degree of injury using Injury Severity Score (ISS) in both groups combined. Further, we examined the WBC as a predictor of serious injury. RESULTS: Our study showed a difference in mean WBC between the two groups that was statistically significant (p<0.001). A positive relationship between ISS and WBC was found, although the association was weak (correlation coefficient = 0.369). While the WBC had moderate discriminatory capability for serious injury, it could not, in isolation, reliably rule in or out serious injury. Nevertheless, this study supports using WBC on presentation to the ED as an adjunct for making disposition decisions. CONCLUSION: A significant elevation in WBC in a blunt trauma patient, even with minimal initial signs of severe injury, should heighten suspicion for occult injury.