Essential Roles of the CC Chemokine Ligand 3-CC Chemokine Receptor 5 Axis in Bleomycin-Induced Pulmonary Fibrosis through Regulation of Macrophage and Fibrocyte Infiltration
Copyright policy )Essential Roles of the CC Chemokine Ligand 3-CC Chemokine Receptor 5 Axis in Bleomycin-Induced Pulmonary Fibrosis through Regulation of Macrophage and Fibrocyte Infiltration
We investigated the pathogenic roles of CC chemokine ligand (CCL)3 and its receptors, CC chemokine receptor (CCR)1 and CCR5, in bleomycin (BLM)-induced pulmonary fibrosis (PF). An intratracheal injection of BLM into wild-type (WT) mice caused a massive infiltration of granulocytes and macrophages, followed by the development of diffuse PF with fibrocyte accumulation. Intrapulmonary CCL3 expression was enhanced rapidly and remained at elevated levels until PF developed. Moreover, CCL3 protein was detected mainly in infiltrating granulocytes and macrophages, whereas transforming growth factor-beta1 protein was detected in macrophages and myofibroblasts. Compared with WT mice, collagen accumulation was reduced in CCL3(-/-) and CCR5(-/-) but not CCR1(-/-) mice. Moreover, the BLM-induced increases in intrapulmonary macrophage and fibrocyte numbers were attenuated in CCL3(-/-) and CCR5(-/-) but not CCR1(-/-) mice, although BLM increased bone marrow (BM) fibrocyte number to a similar extent in these strains. BM transplantation from CCR5(-/-) to WT, but not that from WT to CCR5(-/-) mice, recapitulated the phenotypes in CCR5(-/-) mice. Furthermore, CCR5(+/-) mice exhibited a significant reduction in BLM-induced fibrotic changes. These results demonstrated that locally produced CCL3 was involved in BLM-induced recruitment of BM-derived macrophages and fibrocytes, main producers of transforming growth factor-beta1, and subsequent development of PF by interacting mainly with CCR5.
- University of Tokyo Japan
- Wakayama Medical University Japan
- Kanazawa University Japan
Male, Antibiotics, Antineoplastic, Macrophages, Pulmonary Fibrosis, Fluorescent Antibody Technique, Enzyme-Linked Immunosorbent Assay, Fibroblasts, Macrophage Inflammatory Proteins, Flow Cytometry, Mice, Inbred C57BL, Bleomycin, Chemotaxis, Leukocyte, Mice, Chemokines, CC, Animals, Chemokine CCL4, Chemokine CCL5, In Situ Hybridization, Chemokine CCL3, Granulocytes
Male, Antibiotics, Antineoplastic, Macrophages, Pulmonary Fibrosis, Fluorescent Antibody Technique, Enzyme-Linked Immunosorbent Assay, Fibroblasts, Macrophage Inflammatory Proteins, Flow Cytometry, Mice, Inbred C57BL, Bleomycin, Chemotaxis, Leukocyte, Mice, Chemokines, CC, Animals, Chemokine CCL4, Chemokine CCL5, In Situ Hybridization, Chemokine CCL3, Granulocytes
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).155 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!