Depletion of Collagen IX Alpha1 Impairs Myeloid Cell Function
Autor: | Philipp A. Lang, Haifeng C. Xu, Nikoletta Papadopoulou, Lena Pitzler, Inga von Bomhard, Jacek Stermann, Kristina Probst, Birgit Blissenbach, Alzbeta Machova, Anja Niehoff, Björn Bluhm, Markus Chmielewski, Bent Brachvogel, Hinrich Abken, Julia Etich |
---|---|
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Myeloid Extracellular matrix 03 medical and health sciences Mice 0302 clinical medicine Myeloid Cell Differentiation medicine Animals Humans Myeloid Cells Progenitor cell biology Cell Biology Flow Cytometry Cell biology Fibronectin Haematopoiesis Disease Models Animal 030104 developmental biology medicine.anatomical_structure biology.protein Molecular Medicine Female Bone marrow Collagen Stem cell 030217 neurology & neurosurgery Developmental Biology |
Zdroj: | Stem cells (Dayton, Ohio). 36(11) |
ISSN: | 1549-4918 |
Popis: | The trabecular extracellular matrix (ECM) forms a three-dimensional scaffold to stabilize the bone marrow, provide substrates for cell-matrix interactions and retain, present or release signals to modulate hematopoietic stem and progenitor cell development. However, the impact of trabecular ECM components on hematopoiesis has been poorly studied. Using collagen IX alpha1 - deficient (Col9a1(−/−)) mice, we revealed that a lack of collagen IX alpha1 results in a disorganized trabecular network enriched in fibronectin, and in a reduction in myeloid cells, which was accompanied by a decrease in colony-stimulating factor 1 receptor expression on monocytes from the bone marrow. In contrast, B-cell numbers in the bone marrow and T-cell numbers in the thymus remained unchanged. Alterations in the bone marrow microenvironment may not only reduce myeloid cell numbers, but also have long-term implications for myeloid cell function. Mice were infected with Listeria moncytogenes to analyze the function of myeloid cells. In this case, an inadequate macrophage-dependent clearance of bacterial infections was observed in Col9a1(−/−) mice in vivo. This was mainly caused by an impaired interferon-gamma/tumor necrosis factor-alpha-mediated activation of macrophages. The loss of collagen IX alpha1 therefore destabilizes the trabecular bone network, impairs myeloid cell differentiation, and affects the innate immune response against Listeria. |
Databáze: | OpenAIRE |
Externí odkaz: |