Regulation of proteolysis at the neutrophil-substrate interface by secretory leukoprotease inhibitor.
Human neutrophils can initiate the rapid degradation of extracellular matrix macromolecules by localizing the destructive process to sites of cell-substrate contact. Although plasma and its filtrates contain multiple proteinase inhibitors, these inhibitors did not prevent neutrophils from attacking either underlying fibronectin or elastin. However, subjacent substrates could be protected from neutrophils by recombinant secretory leukoprotease inhibitor, a structurally unique serine proteinase inhibitor whose natural counterpart is normally confined to human mucous secretions. The identification of this extravascular proteinase inhibitor as a potent regulator of subjacent proteolysis could lead to the development of a new class of anti-inflammatory therapeutics.
Rice
W G
WG
Department of Internal Medicine, Simpson Memorial Research Institute, University of Michigan, Ann Arbor 48109.
Weiss
S J
SJ
D002448:Cell Adhesion; D002478:Cells, Cultured; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000378:metabolism*; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D012995:Solubility
D005353:Fibronectins; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D004549:Elastin