<p>Modulation of Human Neutrophil Peptides on <em>P. aeruginosa</em> Killing, Epithelial Cell Inflammation and Mesenchymal Stromal Cell Secretome Profiles</p>

Abstract

ObjectiveNeutrophil infiltration and release of the abundant human neutrophil peptides (HNP) are a common clinical feature in critically ill patients. We tested a hypothesis that different cell types respond to HNP differently in lung microenvironment that may influence the host responses.MethodsPlasma concentrations of HNP were measured in healthy volunteers and patients with sepsis. Cells including the bacteria P. aeruginosa, human lung epithelial cells and mesenchymal stromal cells (MSCs) were exposed to various concentrations of HNP. Bacterial killing, epithelial cell inflammation, MSC adhesion and behaviours were examined after HNP stimulation.ResultsIncubation of P. aeruginosa or stimulation of human lung epithelial cells with HNP resulted in bacterial killing or IL-8 production at a dose of 50 μg/mL, while MSC adhesion and alternations of secretome profiles took place after HNP stimulation at a dose of 10 μg/mL. The secretome profile changes were characterized by increased release of the IL-6 family members such as C-reactive protein (CRP), leukemia inhibitory factor (LIF) and interleukin (IL-11), and first apoptosis signal (FAS) and platelet-derived growth factor-AA as compared to a vehicle control group.ConclusionStimulation of MSCs with HNP resulted in changes of secretome profiles at 5-fold lower concentration than that required for bacterial killing and lung epithelial inflammation. This undisclosed risk factor of HNP in lung environment should be taken into consideration when MSCs are applied as cell therapy in inflammatory lung diseases.

Lactoferrin and Human Neutrophil Protein (HNP) 1–3 Levels During the Neonatal Period in Preterm Infants

“…Human defensins are found at the fetomaternal interface, i.e., amnionic fluid, placenta, ( 8 ) vernix caseosa ( 9 ) and human milk (e.g., lactoferrin (LF) and LL-37) ( 10 ). Other APPs are primarily expressed by neutrophils and reach high systemic levels such as lactoferrin (LF), human neutrophil peptides (HNP) ( 11 ) or bacterial permeability increasing protein (BPI) ( 12 ).…”