Phagocytosis and intracellular digestion of collagen, its role in turnover and remodelling.
Collagens of most connective tissues are subject to continuous remodelling and turnover, a phenomenon which occurs under both physiological and pathological conditions. Degradation of these proteins involves participation of a variety of proteolytic enzymes including members of the following proteinase classes: matrix metalloproteinases (e.g. collagenase, gelatinase and stromelysin), cysteine proteinases (e.g. cathepsin B and L) and serine proteinases (e.g. plasmin and plasminogen activator). Convincing evidence is available indicating a pivotal role for matrix metalloproteinases, in particular collagenase, in the degradation of collagen under conditions of rapid remodelling, e.g. inflammation and involution of the uterus. Under steady state conditions, such as during turnover of soft connective tissues, involvement of collagenase has yet to be demonstrated. Under these circumstances collagen degradation is likely to take place particularly within the lysosomal apparatus after phagocytosis of the fibrils. We propose that this process involves the following steps: (i) recognition of the fibril by membrane-bound receptors (integrins?), (ii) segregation of the fibril, (iii) partial digestion of the fibril and/or its surrounding non-collagenous proteins by matrix metalloproteinases (possibly gelatinase), and finally (iv) lysosomal digestion by cysteine proteinases, such as cathepsin B and/or L. Modulation of this pathway is carried out under the influence of growth factors and cytokines, including transforming growth factor beta and interleukin 1 alpha.
Everts
V
V
Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), The Netherlands.
van der Zee
E
E
Creemers
L
L
Beertsen
W
W
D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003238:Connective Tissue / Q000378:metabolism; D003239:Connective Tissue Cells; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism; D010587:Phagocytosis
D003094:Collagen; D003546:Cysteine Endopeptidases; D008666:Metalloendopeptidases