LEADERSHIP IN FIBROSIS: Scientific Background

Monocyte-lineage cells regulate fibrotic disease processes: Tissue damage generated by disease or injury stimulates the recruitment of monocytes from the blood stream. Once recruited to the site of injury, these monocytes are stimulated to differentiate into one of several basic phenotypes: pro-inflammatory (M1) macrophages, profibrotic (M2) macrophages and fibrocytes, or regulatory macrophages (M_REG), depending upon the cytokines and growth factors found in conjunction with the damaged tissue. In normal healing, equilibrium among these cell types is reached, facilitating the replacement of damaged cells with new cells in the absence of significant scar tissue.

In fibroproliferative diseases, the monocyte-derived cell equilibrium is lost, and monocytes predominantly differentiate into fibrocytes and profibrotic M2 macrophages. These M2 cells recruit and activate large numbers of myofibroblasts to produce the collagen and other proteins that make up scar tissue, as well as release a molecule called TIMP (tissue inhibitor of matrix metalloproteinase) that inhibits scar breakdown as the immune system attempts to wall off the injury. Chronic activation of the myofibroblasts ultimately leads to fibrosis.

There are three primary pathways by which monocyte-lineage cells lead to the initiation, resolution and progression of fibrosis.

[ back to top ]