Proteinases in connective tissue breakdown

Lysosomal cathepsins B and N complete the depolymerization of native fibrillar collagen in the phagolysosome after prior extracellular fragmentation by collagenase and other neutral proteinases. In vitro studies have confirmed that cathepsins B and N cleave native collagen only at the short non-helical telopeptides, which generate the intermolecular cross-links. This action occurs maximally at pH 3.5 and at 37 degrees C the released monomers denature spontaneously and are susceptible to further breakdown. In the phagolysosome the collagenous debris is already weakened and probably therefore, more easily disrupted by these cathepsins. Complete digestion would then be undertaken by the whole complement of proteases. The lysosomal glycosidases may assist this breakdown by degrading ground substance components which are normally tightly bound to collagen. In certain situations cells may instead generate an acidic pericellular environment that could permit the direct action of secreted lysosomal enzymes. This extracellular action may supersede the action of collagenase and the activity of these different enzymes would thus be regulated by changes in the nature of this microenvironment.