Elastase Is the Only Human Neutrophil Granule Protein That Alone Is Responsible for In Vitro Killing of Borrelia burgdorferi

Abstract

Phagocytosis of Borrelia burgdorferi by human polymorphonuclear leukocytes triggers oxygen-dependent and -independent mechanisms of potentially cidal outcome. Nevertheless, no factor or process has yet been singled out as being borreliacidal. We have studied the B. burgdorferi-killing ability of the myeloperoxidase-H2O2-chloride system and that of primary and secondary granule components in an in vitro assay. We found that neither secondary granule acid extracts nor the chlorinating system could kill these microorganisms, while primary granule extracts were effective. The Borrelia-killing factor was purified to homogeneity and demonstrated to be elastase. Its cidal activity was found to be independent of its proteolytic activity.

Super-silent FRET Sensor Enables Live Cell Imaging and Flow Cytometric Stratification of Intracellular Serine Protease Activity in Neutrophils

“…Intracellular seprocidin activity is required for killing of bacteria within the neutrophil 3 , 17 – 19 . Based on the propensity of dendrimeric scaffolds to carry cargoes into cells 20 , 21 , the intracellular visualisation of serprocidin activity was explored.…”

How human neutrophils kill and degrade microbes: an integrated view

“…Of interest, the augmented killing is not compromised by heat‐inactivating HNE enzymatic activity, suggesting that elastolytic action is not a prerequisite for synergy. The independence of anti‐microbial action from enzymatic activity has been observed in studies of PMN– Borrelia interactions (72) and applies to other serprocidins, including cathepsin G (33, 73). Given the cationic nature common to this group of granule proteins, it is reasonable to speculate that their strong electrostatic interactions with the microbial surface disrupt the integrity of the organism, rendering potential targets more accessible to attack.…”

Internalization of Proteinase 3 Is Concomitant with Endothelial Cell Apoptosis and Internalization of Myeloperoxidase with Generation of Intracellular Oxidants

“…Elastase has a death function separable from and independent of its proteolytic activity. 43 It has recently been shown that azurocidin is internalized into endothelial cells and is targeted to mitochondrial compartments of the cell, but not in the nuclear compartment. 44 Interestingly, internalized azurocidin markedly reduces growth factor deprivation-induced apoptosis, and the authors have suggested that uptake of exogenous azurocidin contributes to the sustained viability of endothelial cells in the context of locally activated neutrophils.…”