Trauma Induces Emergency Hematopoiesis through IL-1/MyD88–Dependent Production of G-CSF

Fuchs, Anja; Monlish, Darlene; Ghosh, Subham; Chang, Soo-Eun; Bochicchio, Grant V.; Schuettpelz, Laura G.; Turnbull, Isaiah R.

doi:10.4049/jimmunol.1801456

Cited by 29 publications

(24 citation statements)

References 44 publications

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“…Consistently, these parameters are lower in the sero-low COVID19 patients, with mean values toward the low end of normal ranges ( Supplementary file 1 ), but increase significantly in sero-high patients. These changes are indicative of an early but transient depletion of lymphocytes, neutrophils, and platelets in COVID19, followed by ‘emergency hematopoiesis’, a compensatory phenomenon involving broad stimulation of hematopoietic and stem cell progenitors (HSPCs) by factors such as G-CSF (CSF3) ( Fuchs et al, 2019 ), which we found to be elevated in sero-low patients ( Figure 3a ). The oscillations in neutrophils and lymphocyte counts could explain some of the changes in soluble immune factors depleted in sero-low patients only (e.g.…”

Section: Resultsmentioning

confidence: 90%

Seroconversion stages COVID19 into distinct pathophysiological states

Galbraith

Kinning

Sullivan

et al. 2021

eLife

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COVID19 is a heterogeneous medical condition involving diverse underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging biomarkers hamper the ability to stratify patients for targeted therapeutics. We report here the results of a cross-sectional multi-omics analysis of hospitalized COVID19 patients revealing that seroconversion status associates with distinct underlying pathophysiological states. Low antibody titers associate with hyperactive T cells and NK cells, high levels of IFN alpha, gamma and lambda ligands, markers of systemic complement activation, and depletion of lymphocytes, neutrophils, and platelets. Upon seroconversion, all of these processes are attenuated, observing instead increases in B cell subsets, emergency hematopoiesis, increased D-dimer, and hypoalbuminemia. We propose that seroconversion status could potentially be used as a biosignature to stratify patients for therapeutic intervention and to inform analysis of clinical trial results in heterogenous patient populations.

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Section: Resultsmentioning

confidence: 90%

Seroconversion stages COVID19 into distinct pathophysiological states

Galbraith

Kinning

Sullivan

et al. 2021

eLife

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“…Enhanced HSPC proliferation after sham injury or SCI may represent a compensatory response to the stress of blood loss and trauma. Indeed, both psychological and physical stressors enhance bone marrow hematopoiesis and extramedullary hematopoiesis in secondary lymphoid tissues, including the spleen 4,[33][34][35][36][37] .…”

Section: Resultsmentioning

confidence: 99%

Spinal cord injury causes chronic bone marrow failure

et al. 2020

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Spinal cord injury (SCI) causes immune dysfunction, increasing the risk of infectious morbidity and mortality. Since bone marrow hematopoiesis is essential for proper immune function, we hypothesize that SCI disrupts bone marrow hematopoiesis. Indeed, SCI causes excessive proliferation of bone marrow hematopoietic stem and progenitor cells (HSPC), but these cells cannot leave the bone marrow, even after challenging the host with a potent inflammatory stimulus. Sequestration of HSPCs in bone marrow after SCI is linked to aberrant chemotactic signaling that can be reversed by post-injury injections of Plerixafor (AMD3100), a small molecule inhibitor of CXCR4. Even though Plerixafor liberates HSPCs and mature immune cells from bone marrow, competitive repopulation assays show that the intrinsic long-term functional capacity of HSPCs is still impaired in SCI mice. Together, our data suggest that SCI causes an acquired bone marrow failure syndrome that may contribute to chronic immune dysfunction.

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“…Consistently, these parameters are lower in the seronegative COVID19 patients, but return to baseline levels in seroconverted patients. These changes are indicative of an early but transient round of neutropenia, thrombocytopenia and lymphopenia in COVID19, followed by ‘emergency hematopoiesis’, a compensatory phenomenon involving broad stimulation of hematopoietic and stem cell progenitors (HSPCs) by factors such as G-CSF (CSF3) (19), which we found to be elevated in seronegative patients ( Fig. 3a ) The oscillations in neutrophils and lymphocyte counts could explain some of the changes in soluble immune factors depleted in seronegative patients only (e.g.…”

Section: Resultsmentioning

confidence: 99%

Seroconversion stages COVID19 into distinct pathophysiological states

Galbraith

Kinning

Sullivan

et al. 2020

Preprint

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COVID19 is a heterogeneous medical condition involving a suite of underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging biomarkers hamper the ability to stratify patients for targeted therapeutics. We report here the results of a cross-sectional multi-omics analysis of hospitalized COVID19 patients revealing that seroconversion status associates with distinct underlying pathophysiological states. Seronegative COVID19 patients harbor hyperactive T cells and NK cells, high levels of IFN alpha, gamma and lambda ligands, markers of systemic complement activation, neutropenia, lymphopenia and thrombocytopenia. In seropositive patients, all of these processes are attenuated, observing instead increases in B cell subsets, emergency hematopoiesis, increased markers of platelet activation, and hypoalbuminemia. We propose that seroconversion status could potentially be used as a biosignature to stratify patients for therapeutic intervention and to inform analysis of clinical trial results in heterogenous patient populations.

show abstract

Trauma Induces Emergency Hematopoiesis through IL-1/MyD88–Dependent Production of G-CSF

Cited by 29 publications

References 44 publications

Seroconversion stages COVID19 into distinct pathophysiological states

Seroconversion stages COVID19 into distinct pathophysiological states

Spinal cord injury causes chronic bone marrow failure

Seroconversion stages COVID19 into distinct pathophysiological states

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