Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism.
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Normally, neutrophil pools are maintained by homeostatic mechanisms that require the transcription factor C/EBPα. Inflammation, however, induces neutrophilia through a distinct pathway of "emergency" granulopoiesis that is dependent on C/EBPβ. Here, we show in mice that alum triggers emergency granulopoiesis through the IL-1RI-dependent induction of G-CSF. G-CSF/G-CSF-R neutralization impairs proliferative responses of hematopoietic stem and progenitor cells (HSPC) to alum, but also abrogates the acute mobilization of BM neutrophils, raising the possibility that HSPC responses to inflammation are an indirect result of the exhaustion of BM neutrophil stores. The induction of neutropenia, via depletion with Gr-1 mAb or myeloid-specific ablation of Mcl-1, elicits G-CSF via an IL-1RI-independent pathway, stimulating granulopoietic responses indistinguishable from those induced by adjuvant. Notably, C/EBPβ, thought to be necessary for enhanced generative capacity of BM, is dispensable for increased proliferation of HSPC to alum or neutropenia, but plays a role in terminal neutrophil differentiation during granulopoietic recovery. We conclude that alum elicits a transient increase in G-CSF production via IL-1RI for the mobilization of BM neutrophils, but density-dependent feedback sustains G-CSF for accelerated granulopoiesis.
Enzyme-Linked Immunosorbent Assay
Granulocyte Colony-Stimulating Factor
Hematopoietic Stem Cells
Mice, Inbred C57BL
Published Version (Please cite this version)10.1371/journal.pone.0019957
Publication InfoCain, Derek W; Snowden, Pilar B; Sempowski, Gregory D; & Kelsoe, Garnett (2011). Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism. PLoS One, 6(5). pp. e19957. 10.1371/journal.pone.0019957. Retrieved from https://hdl.handle.net/10161/10903.
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Assistant Professor in Medicine
My research focuses on the interactions of T cells and B cells during infection or following vaccination. I am particularly interested in the inter- and intracellular events that take place within germinal centers, the anatomic site of antibody evolution during an immune response.
James B. Duke Distinguished Professor of Immunology
1. Lymphocyte development and antigen-driven diversification of immunoglobulin and T cell antigen receptor genes. 2. The germinal center reaction and mechanisms for clonal selection and self - tolerance. The origins of autoimmunity. 3. Interaction of innate- and adaptive immunity and the role of inflammation in lymphoid organogenesis. 4. The role of secondary V(D)J gene rearrangment in lymphocyte development and malignancies. 5. Mathematical modeling of immune responses,
Professor in Medicine
Dr. Sempowski earned his PhD in Immunology from the University of Rochester and was specifically trained in the areas of inflammation, wound healing, and host response (innate and adaptive). Dr. Sempowski contributed substantially to the field of lung inflammation and fibrosis defining the roles of pulmonary fibroblast heterogeneity and CD40/CD40L signaling in regulating normal and pathogenic lung inflammation. During his postdoctoral training with Dr. Barton F. H
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