P , Lorkowski J Production of type VI collagen by human macrophages: a new dimension in macrophage functional heterogeneity

Macrophages derived from human blood monocytes perform many tasks related to tissue injury and repair. The main effect of macrophages on the extracellular matrix is considered to be destructive in nature, because macrophages secrete metalloprotein-ases and ingest foreign material as part of the remodeling process that occurs in wound healing and other pathological conditions. However, macrophages also contribute to the extracellular matrix and hence to tissue stabilization both indirectly, by inducing other cells to proliferate and to release matrix components, and directly, by secreting components of the extracellular matrix such as fibronectin and type VIII collagen, as we have recently shown. We now report that monocytes and macrophages express virtually all known collagen and collagen-related mRNAs. Furthermore, macrophages secrete type VI collagen protein abun-dantly, depending upon their mode of activation, stage of differentiation, and cell density. The primary function of type VI collagen secreted by macrophages appears to be modulation of cell-cell and cell-matrix interactions. We suggest that the production of type VI collagen is a marker for a nondestructive, matrix-conserving macrophage phenotype that could profoundly influence physi-ological and pathophysiological conditions in vivo. The Journal of Immunology, 2008, 180: 5707–5719. A dult macrophages are the phagocytotic cells of the cel-lular immune system (1). They are derived from circu-lating blood monocytes that leave the blood and become resident in tissues. Recruitment of monocytes to peripheral tissues increases when the cells are exposed to proinflammatory stimuli. Inside tissues, monocytes differentiate into macrophages, includin