The role of fibrocytes in fibrotic diseases of the lungs and heart

Fibrosis is the end result of a complex series of events that follow tissue injury and inflammation. If this process is faulty, excessive matrix deposition occurs and normal tissue is replaced with permanent scar, resulting in organ dysfunction. Fibrocytes are circulating bone-marrow-derived progenitor cells that were first identified in the context of an experimental model of wound repair [1], and have since been shown to play a pivotal role in both normal and aberrant healing in humans [2]. The striking similarities seen in fibroproliferative processes involving both the lungs and the heart has brought about the possibility of a common etiologic mechanism [3]. In this review, we focus on a unique mesenchymal progenitor cell, the fibrocyte, as the potential common denominator in fibrotic diseases affecting the lungs and the heart.Fibrocytes were originally described when investigators noted the early appearance of spindle-shaped cells that expressed collagen, procollagen and CD34 in an experimental skin wound repair model [1]. Their appearance in the wound chamber, within 1 day after injury, was much earlier than would be expected by entry of fibroblasts from the surrounding skin, and therefore these cells were thought to originate from the circulation. Thus, the investigators coined the word 'fibrocyte', a combination of 'fibroblast' and 'leukocyte'. In healthy humans, fibrocytes comprise 0.1-1.0% of nucleated cells in peripheral blood, and have been found in a variety of tissues in both healthy and diseased states [4-6].Fibrocytes perform diverse functions that are important in normal tissue repair and fibrosis. In addition to mediating fibrogenesis by secreting inflammatory cytokines, chemokines and growth factors [4,7], fibrocytes also constitutively produce extracellular matrix proteins (collagen I, collagen III and vimentin) and secrete matrix metalloproteinases [7]. In addition, they play a role in the recruitment and activation of T cells as antigen-present