AI Article Synopsis

  • Polymorphonuclear neutrophils (PMNs) are crucial for immune defense and help connect innate and adaptive immunity, using proteolytic enzymes like MT6-MMP (MMP-25) for their functions.
  • Research shows that MT6-MMP is found in various cellular compartments of PMNs and is secreted when they are stimulated, but it remains anchored in membrane lipid rafts during rest and does not appear on the cell surface until apoptosis occurs.
  • The study indicates that while MT6-MMP may influence respiratory bursts and IL-8 secretion, it does not affect chemotaxis or survival induced by granulocyte macrophage colony-stimulating factor, providing new insights into its role in

Article Abstract

Polymorphonuclear neutrophils (PMNs) are the first line of defense against invading organisms in humans; in addition, PMNs contribute to the linking of innate and adaptive immunity. To fulfill their biological behavior, PMNs utilize an arsenal of proteolytic enzymes, including members of the matrix metalloproteinase family of zinc-dependent endopeptidases. PMNs express high levels of MT6-MMP (MMP-25), a glycosyl-phosphatidylinositol-anchored MMP, that belongs to the subfamily of membrane-anchored matrix metalloproteinases. Due to the paucity of information on MT6-MMP in primary cells, we set to investigate the localization and potential function of MT6-MMP in human PMNs. We found that MT6-MMP is present in the membrane, granules and nuclear/endoplasmic reticulum/Golgi fractions of PMNs where it is displayed as a disulfide-linked homodimer of 120 kDa. Stimulation of PMNs resulted in secretion of active MT6-MMP into the supernatants. Membrane-bound MT6-MMP, conversely, is located in the lipid rafts of resting PMNs and stimulation does not alter this location. In addition, TIMP-2, a natural inhibitor of MT6-MMP, does not co-localize with it in the lipid rafts. Interestingly, living PMNs do not display MT6-MMP on the cell surface. However, induction of apoptosis induces MT6-MMP relocation on PMNs' cell surface. Our studies suggest that metalloproteinases may play a role in respiratory burst and IL-8 secretion, but not chemotaxis or granulocyte macrophage colony-stimulating factor-induced survival. Collectively, these results provide new insights on the role of MT6-MMP in the physiology of human PMNs.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915617PMC
http://dx.doi.org/10.1093/intimm/dxq048DOI Listing

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