Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:Q99581 (
FEV
)
3,296
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Severe asthma is typically characterized by chronic airway inflammation that is refractory to corticosteroids and associated with excess morbidity. Patients were recruited into the National Heart, Lung, and Blood Institute-sponsored Severe Asthma Research Program and comprehensively phenotyped by bronchoscopy. Bronchoalveolar lavage (BAL) cells were analyzed by flow cytometry. Compared with healthy individuals (
n
= 21), patients with asthma (
n
= 53) had fewer BAL natural killer (NK) cells. Patients with severe asthma (
n
= 29) had a marked increase in the ratios of CD4
+
T cells to NK cells and neutrophils to NK cells. BAL NK cells in severe asthma were skewed toward the cytotoxic CD56
dim
subset, with significantly increased BAL fluid levels of the cytotoxic mediator
granzyme A
. The numbers of BAL CD56
dim
NK cells and CCR6
-
CCR4
-
T helper 1-enriched CD4
+
T cells correlated inversely with lung function [forced expiratory volume in 1 s (
FEV
1
) % predicted] in asthma. Relative to cells from healthy controls, peripheral blood NK cells from asthmatic patients had impaired killing of K562 myeloid target cells despite releasing more cytotoxic mediators. Ex vivo exposure to dexamethasone markedly decreased blood NK cell lysis of target cells and cytotoxic mediator release. NK cells expressed airway lipoxin A
4
/formyl peptide receptor 2 receptors, and in contrast to dexamethasone, lipoxin A
4
-exposed NK cells had preserved functional responses. Together, our findings indicate that the immunology of the severe asthma airway is characterized by decreased NK cell cytotoxicity with increased numbers of target leukocytes, which is exacerbated by corticosteroids that further disable NK cell function. These failed resolution mechanisms likely contribute to persistent airway inflammation in severe asthma.
...
PMID:Natural killer cell-mediated inflammation resolution is disabled in severe asthma. 2878 2
