Cellular Plasticity of Inflammatory Myeloid Cells in the Peritoneal Foreign Body Response

• Published in: The American journal of pathology Vol. 176; no. 1; pp. 369 - 380
• Main Authors: Mooney, Jane E, Rolfe, Barbara E, Osborne, Geoffrey W, Sester, David P, van Rooijen, Nico, Campbell, Gordon R, Hume, David A, Campbell, Julie H
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 2010; ASIP; American Society for Investigative Pathology
• Subjects: Animals; Biological and medical sciences; Cell Movement; Cell Shape; Cell Transdifferentiation; Female; Fibroblasts - cytology; Foreign Bodies - pathology; Foreign-Body Reaction - pathology; Green Fluorescent Proteins - metabolism; Implants, Experimental; Investigative techniques, diagnostic techniques (general aspects); Macrophages - cytology; Male; Medical sciences; Mice; Myeloid Cells - pathology; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Peritoneal Cavity - pathology; Peritoneal Lavage; Regular; Anatomic pathology; Plasticity; Foreign body; Inflammation; Inflammatory cell; Myeloid cell; Peritoneum
• ISSN: 0002-9440; 1525-2191
• DOI: 10.2353/ajpath.2010.090545

Implantation of sterile foreign objects in the peritoneal cavity of an animal initiates an inflammatory response and results in encapsulation of the objects by bone marrow-derived cells. Over time, a multilayered tissue capsule develops with abundant myofibroblasts embedded in extracellular matrix. The present study used the transgenic MacGreen mouse to characterize the time-dependent accumulation of monocyte subsets and neutrophilic granulocytes in the inflammatory infiltrate and within the tissue capsule by their differential expression of the csf1r -EGFP transgene, F4/80, and Ly6C. As the tissue capsule developed, enhanced green fluorescent protein-positive cells changed from rounded to spindle-shaped morphology and began to co-express the myofibroblast marker α-smooth muscle actin. Expression increased with time: at day 14, 11.13 ± 0.67% of tissue capsule cells co-expressed these markers, compared with 50.77 ± 12.85% of cells at day 28. The importance of monocyte/macrophages in tissue capsule development was confirmed by clodronate-encapsulated liposome removal, which resulted in almost complete abrogation of capsule development. These results confirm the importance of monocyte/macrophages in the tissue response to sterile foreign objects implanted in the peritoneal cavity. In addition, the in vivo plasticity of peritoneal macrophages and their ability to transdifferentiate from a myeloid to mesenchymal phenotype is demonstrated.