Neutrophil Microparticles Deliver Active Myeloperoxidase to Injured Mucosa To
Inhibit Epithelial Wound Healing
#MMPMID28242649
Slater TW
; Finkielsztein A
; Mascarenhas LA
; Mehl LC
; Butin-Israeli V
; Sumagin R
J Immunol
2017[Apr]; 198
(7
): 2886-2897
PMID28242649
show ga
Neutrophil (PMN) infiltration of the intestinal mucosa often leads to severe
epithelial injury; however, how this process occurs is unclear. This article
describes a novel mechanism whereby membrane-derived microparticles released by
tissue infiltrating PMNs (PMN-MPs) serve as shuttles to protect and deliver
active mediators to locally modulate cellular function during inflammation.
Specifically, myeloperoxidase (MPO), which is abundantly expressed in PMN
azurophilic granules and is used for microbial killing, was found to be mobilized
to the PMN surface and subsequently released in association with PMN-MPs upon PMN
activation and binding to intestinal epithelial cells (IECs). The enzymatic
activity of PMN-MP-associated MPO was enhanced compared with soluble protein,
leading to potent inhibition of wound closure following PMN-MP binding to IECs.
Importantly, localized microinjection of PMN-MPs into wounded colonic mucosa was
sufficient to impair epithelial wound healing in vivo. PMN-MP/MPO-dependent
inhibition of IEC wound healing was due to impaired IEC migration and
proliferation, resulting from impeded actin dynamics, cell spreading, and cell
cycle arrest. Thus, our findings provide new insight into mechanisms governing
PMN-induced tissue injury and implicate PMN-MPs and MPO as important regulators
of cellular function.
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