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Calprotectin promotes anemia of inflammation in healthy and pathological conditions

ABSTRACT: Elevated circulating levels of calprotectin (CAL), the S100A8/A9 heterodimer, are biomarkers of severe systemic inflammation. Here, we investigate the effects of CAL on early human hematopoiesis. CAL demonstrates limited impact on gene expression in stem and progenitor cells, in contrast with interleukin-6 (IL6) that promotes the expression of the S100A8 and S100A9 genes in hematopoietic progenitors and the generation of monocytes that release CAL. The main target of CAL is an erythroid-megakaryocyte progenitor (EMP) subset. CAL prevents both erythropoietin-driven differentiation of healthy progenitors and JAK2-V617F-driven erythropoiesis. In the context of JAK2-V617F, CAL also promotes the expression of S100A8 and S100A9 genes in monocytes. The signature of CAL effects is detected in the bone marrow progenitors of patients with myeloid malignancy or severe infection. These results position CAL as a mediator of IL6 effects on triggering anemia during inflammation, an effect that is amplified in the context of JAK2-V617F-driven hematopoiesis.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Bone Marrow, Erythroblast

SUBMITTER: Marjorie Leduc

LAB HEAD: Eric Solary

PROVIDER: PXD057999 | Pride | 2024-11-20

REPOSITORIES: Pride

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			Action	DRS
	ErSO230531_ClapIL6_10_J12_A50804_RD10_1_10881.d.7z	Other
	ErSO230531_ClapIL6_11_J12_A50805_RD11_1_10893.d.7z	Other
	ErSO230531_ClapIL6_12_J12_CALPRO_A50806_RD12_1_10887.d.7z	Other
	ErSO230531_ClapIL6_13_J12_CALPRO_A50807_RD13_1_10899.d.7z	Other
	ErSO230531_ClapIL6_14_J15_A50808_RD14_1_10883.d.7z	Other

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