Mast cells mediate Pseudomonas aeruginosa lipopolysaccharide-induced lung inflammation in rat

Abstract

Activated mast cells have been demonstrated to play a pivotal role in Pseudomonas aeruginosa lung infections. However, there is no report about the involvement of mast cells in P. aeruginosa lipopolysaccharide (LPS)-induced lung inflammation. This study aimed at evaluating the role of mast cells in P. aeruginosa LPS-induced lung inflammation in rats. Mast cells stabilization was carried out by intraperitoneal injections of cromolyn. Lung inflammation was induced by the intratracheal instillation of P. aeruginosa LPS (5 μg/kg bw) and inflammatory status was evaluated 4 h post-LPS instillation. We found that activated mast cells could constitute a pivotal source of several inflammatory cytokines, including TNF-α, IL-1β, and IL-6. These cells might regulate polymorphonuclear neutrophil (PMN) recruitment and be implicated in the alteration of alveolar-capillary permeability via the release of TNF-α and IL-1β. We also detected that activated mast cells could be involved in the alteration of the expression of two epithelial tight junction proteins (claudin-1 and occludin) during the acute phase of inflammation. Our results suggest that activated mast cells might play a critical role in P. aeruginosa LPS-induced lung inflammation. Therefore, mast cell stabilization may be a potential novel approach for the prevention and treatment of P. aeruginosa-induced lung infections.

Autophagy Enhances Bacterial Clearance during P. aeruginosa Lung Infection

“…Given the well characterized central role of autophagy in the clearance of intracellular pathogens [25], and the observation that autophagy is impaired in the airways of cystic fibrosis patients, we set out to examine the role of autophagy in host defense against P. aeruginosa in vivo , and explored the therapeutic potential of pharmacological manipulation of the autophagy pathway during P. aeruginosa lung infection. Our results demonstrate that P. aeruginosa infection induces autophagy in mast cells which are abundant in the airways where they play a central role in host defense against P. aeruginosa [5], [7], as well as in bronchial epithelial cells which have been proposed to act as a reservoir of intracellular bacteria during chronic P. aeruginosa infection [24], [26], [27], [28], [29]. We further demonstrated that inhibition of the autophagy pathway significantly impairs clearance of P. aeruginosa from mast cells and human bronchial epithelial cells, while induction of the process enhances bacterial killing.…”

“…Mast cells are important sentinel cells of the immune system, playing a critical role in sensing invading pathogens and coordinating the appropriate immune response against P. aeruginosa [5], [7]. Due to the high density of the cells along the airways, and their phagocyte capacity, mast cells also represent the first line of defense against pathogens within the respiratory tract.…”

“…In healthy individuals P. aeruginosa infection triggers strong inflammatory responses, mediated largely through TLR signaling pathways, which lead to neutrophil recruitment and effective clearance of the bacteria [2]. The coordination of these early host responses to the pathogen are largely mediated by resident immune cells in the airway such as mast cells or alveolar macrophages [3], [4], [5]. Mast cells are recognized as sentinel cells of the immune system in the respiratory tract where they represent up to 2% of the alveolar wall and protrude into the airspace of the lung where they are ideally placed to be first responders to invading pathogens [6].…”

Zingerone Suppresses Liver Inflammation Induced by Antibiotic Mediated Endotoxemia through Down Regulating Hepatic mRNA Expression of Inflammatory Markers in Pseudomonas aeruginosa Peritonitis Mouse Model

“…Endotoxin, which is a hydrophobic glycolipid, is known to play a very imperative role in pathogenesis of P. aeruginosa mediated infections [4], [5], [6]. It is well recognized that cell free endotoxin is significantly more biologically functional than cell bound endotoxin and antibiotics, particularly those that act as inhibitors of cell wall biosynthesis, induce enormous amount of endotoxin release during treatment [7].…”

Mast Cells Play an Important Role in Chlamydia pneumoniae Lung Infection by Facilitating Immune Cell Recruitment into the Airway

“…In the EAE model of multiple sclerosis, mast cells in the dura mater and pia mater exacerbate the inflammation by facilitating neutrophil recruitment and promoting blood brain barrier and CSF-blood barrier breakdown to allow immune cells access to the CNS (19–21). Additionally, in a Pseudomonas LPS model of pulmonary inflammation, mast cells mediated the influx of neutrophils into the lung (12, 24–29). One possible mechanism for the control of neutrophil infiltration into the lungs was by controlling TREM-1 expression on neutrophils.…”