Production of Type VI Collagen by Human Macrophages: A New Dimension in Macrophage Functional Heterogeneity

TLDR

Human blood monocyte‑derived macrophages play diverse roles in tissue injury and repair, traditionally viewed as destructive through metalloproteinase secretion, yet they also stabilize the extracellular matrix by producing matrix components such as fibronectin and type VIII collagen. The study proposes that type VI collagen production marks a nondestructive, matrix‑conserving macrophage phenotype that could profoundly influence physiological and pathophysiological conditions in vivo. Monocytes and macrophages express nearly all collagen and collagen‑related mRNAs and secrete abundant type VI collagen, whose primary role is to modulate cell‑cell and cell‑matrix interactions, with secretion levels varying by activation state, differentiation stage, and cell density.

Abstract

Abstract 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 metalloproteinases 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 abundantly, 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 physiological and pathophysiological conditions in vivo.