Defining the contractile prostanoid component in hyperosmolar-induced bronchoconstriction in human small airways.

Exercise-induced bronchoconstriction (EIB) is thought to be triggered by increased osmolarity at the airway epithelium. The aim of this study was to define the contractile prostanoid component of EIB, using an ex vivo model where intact segments of bronchi (inner diameter 0.5-2 mm) isolated from human lung tissue and subjected to mannitol.

Analysis of human lung mast cells by single cell RNA sequencing.

Mast cells are tissue-resident cells playing major roles in homeostasis and disease conditions. Lung mast cells are particularly important in airway inflammatory diseases such as asthma. Human mast cells are classically divided into the subsets MC and MC, where MC express the mast cell protease tryptase and MC in addition express chymase, carboxypeptidase A3 (CPA3) and cathepsin G.

Cysteinyl-maresin 3 inhibits IL-13 induced airway hyperresponsiveness through alternative activation of the CysLT receptor.

Background: Cysteinyl-maresins, also known as maresin-conjugates in tissue regeneration (MCTRs), are recently discovered lipid mediators proposed to reduce airway inflammation.

Objective: To investigate the influence of MCTRs on IL-13-induced airway hyperresponsiveness in isolated human and mice airways.

Methods: Before responsiveness to contractile agonists were assessed in myographs, human small bronchi were cultured for 2 days and mouse tracheas were cultured for 1-4 days.

Immunoprofiling Reveals Novel Mast Cell Receptors and the Continuous Nature of Human Lung Mast Cell Heterogeneity.

Background: Immunohistochemical analysis of granule-associated proteases has revealed that human lung mast cells constitute a heterogeneous population of cells, with distinct subpopulations identified. However, a systematic and comprehensive analysis of cell-surface markers to study human lung mast cell heterogeneity has yet to be performed.

Methods: Human lung mast cells were obtained from lung lobectomies, and the expression of 332 cell-surface markers was analyzed using flow cytometry and the LEGENDScreen™ kit.

Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing.

The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127 ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs.

IL-13 and IL-4, but not IL-5 nor IL-17A, induce hyperresponsiveness in isolated human small airways.

Background: Specific inflammatory pathways are indicated to contribute to severe asthma, but their individual involvement in the development of airway hyperresponsiveness remains unexplored.

Objective: This experimental study in human small bronchi aimed to provide insight into which of the type 2 and type 17 cytokines cause hyperresponsiveness of airway smooth muscle.

Methods: Explanted small bronchi isolated from human lung tissue and human airway smooth muscle cells were treated for 2 and 1 day(s), respectively, with 100 ng/mL of IL-4, IL-5, IL-13, or IL-17A, and contractile responses, Ca mobilization, and receptor expression were assessed.

Mannitol triggers mast cell-dependent contractions of human small bronchi and prostacyclin bronchoprotection.

Background: Clinical research supports that exercise-induced bronchoconstriction (EIB) is caused by hyperosmolar triggering of mast cells. The reaction can be mimicked by inhalation of mannitol, but it has paradoxically previously not been possible to replicate this mode of action of mannitol in isolated airways.

Objective: We sought to establish an ex vivo model of EIB in human small bronchi.

An Optimized Protocol for the Isolation and Functional Analysis of Human Lung Mast Cells.

Mast cells are tissue-resident inflammatory cells defined by their high granularity and surface expression of the high-affinity IgE receptor, FcεRI, and CD117/KIT, the receptor for stem cell factor (SCF). There is a considerable heterogeneity among mast cells, both phenotypically and functionally. Human mast cells are generally divided into two main subtypes based on their protease content; the mucosa-associated MC (tryptase positive and chymase negative mast cell) and the connective tissue associated-residing MC (tryptase and chymase positive mast cell).

Human lung natural killer cells are predominantly comprised of highly differentiated hypofunctional CD69CD56 cells.

Background: In contrast to the extensive knowledge about human natural killer (NK) cells in peripheral blood, relatively little is known about NK cells in the human lung. Knowledge about the composition, differentiation, and function of human lung NK cells is critical to better understand their role in diseases affecting the lung, including asthma, chronic obstructive pulmonary disease, infections, and cancer.

Objective: We sought to analyze and compare the phenotypic and functional characteristics of NK cells in the human lung and peripheral blood at the single-cell level.

Prostaglandin E2 inhibits mast cell-dependent bronchoconstriction in human small airways through the E prostanoid subtype 2 receptor.

Background: Inhaled prostaglandin (PG) E2 might inhibit asthmatic responses, but the mechanisms involved remain undefined.

Objective: We sought to characterize the direct and indirect effects of PGE2 on human small airways with particular reference to the receptors mediating the responses.

Methods: Contraction and relaxation were studied in isolated human bronchi with an inner diameter of 1 mm or less.

Bitter taste receptor agonists mediate relaxation of human and rodent vascular smooth muscle.

Taste-sensing type 2 receptors (TAS2Rs) have been implicated in extraoral functions. Airway smooth muscle expresses TAS2Rs and is strongly relaxed by TAS2R agonists. We hypothesised that TAS2R agonists might affect vascular smooth muscle as well.