apyrase and Pneumonia

Topics: Adenosine Triphosphate; Apyrase; Bleomycin; Humans; Hydrolysis; Phagocytes; Pneumonia

Topics: Antiviral Agents; Apyrase; B-Lymphocytes; B7-H1 Antigen; Betacoronavirus; Case-Control Studies; Coronavirus Infections; COVID-19; Gene Expression; Humans; Immunologic Factors; Killer Cells, Natural; Molecular Targeted Therapy; NK Cell Lectin-Like Receptor Subfamily C; Pandemics; Pneumonia; Pneumonia, Viral; Programmed Cell Death 1 Receptor; SARS-CoV-2; Severe Acute Respiratory Syndrome; T-Lymphocyte Subsets

Adenosine triphosphate (ATP) is a key mediator to alert the immune dysfunction by acting on P2 receptors. Here, we found that allergen challenge caused an increase of ATP secretion in a murine model of neutrophilic asthma, which correlated well with neutrophil counts and interleukin-17 production. When ATP signaling was blocked by intratracheal administration of the ATP receptor antagonist suramin before challenge, neutrophilic airway inflammation, airway hyperresponsiveness, and Th17-type responses were reduced significantly. Also, neutrophilic inflammation was abrogated when airway ATP levels were locally neutralized using apyrase. Furthermore, ATP promoted the Th17 polarization of splenic CD4

Topics: Adenosine Triphosphate; Allergens; Animals; Apyrase; Asthma; Cell Differentiation; Cells, Cultured; Disease Models, Animal; Female; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neutrophils; Ovalbumin; Pneumonia; Purinergic P2 Receptor Antagonists; Receptors, Antigen, T-Cell, alpha-beta; Suramin; T-Lymphocyte Subsets; Th17 Cells

Purinergic receptor activation via extracellular ATP is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Nucleoside triphosphate diphosphohydrolase-1/CD39 hydrolyses extracellular ATP and modulates P2 receptor signalling.We aimed to investigate the expression and function of CD39 in the pathogenesis of cigarette smoke-induced lung inflammation in patients and preclinical mouse models. CD39 expression and soluble ATPase activity were quantified in sputum and bronchoalveolar lavage fluid (BALF) cells in nonsmokers, smokers and COPD patients or mice with cigarette smoke-induced lung inflammation. In mice, pulmonary ATP and cytokine concentrations, inflammation and emphysema were analysed in the presence or absence of CD39.Following acute cigarette smoke exposure CD39 was upregulated in BALF cells in smokers with further increases in COPD patients. Acute cigarette smoke exposure induced CD39 upregulation in murine lungs and BALF cells, and ATP degradation was accelerated in airway fluids. CD39 inhibition and deficiency led to augmented lung inflammation; treatment with ATPase during cigarette smoke exposure prevented emphysema.Pulmonary CD39 expression and activity are increased in COPD. CD39 deficiency leads to enhanced emphysema in mice, while external administration of a functional CD39 analogue partially rescues the phenotype. The compensatory upregulation of pulmonary CD39 might serve as a protective mechanism in cigarette smoke-induced lung damage.

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Adult; Animals; Antigens, CD; Apyrase; Bronchoalveolar Lavage Fluid; Chemokine CXCL2; Cytokines; Female; Humans; Immunohistochemistry; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Nicotiana; Pneumonia; Pulmonary Disease, Chronic Obstructive; Real-Time Polymerase Chain Reaction; Receptors, Purinergic P2; Signal Transduction; Smoke; Smoking; Spumavirus; Young Adult

γδ T cells have been shown to have immunoregulatory functions in several experimental autoimmune models. A mutation of the Foxp3 gene leads to the absence of regulatory T cells (Tregs) and a fatal systemic autoimmune disease in scurfy mice. Transfer of scurfy lymphocytes to RAG deficient (RAG(-/-)) recipients reproduces the inflammatory phenotype of the scurfy donor, including hepatitis and pneumonitis. In this study, we show that TCRα(-/-) recipients, which lack αβ T cells but have γδ T cells and B cells, are significantly protected from the hepatitis and pneumonitis, but not the dermatitis, induced by adoptive transfer of scurfy lymphocytes. Cotransfer of γδ T cells, but not B cells, prevented hepatitis and pneumonitis in RAG(-/-) recipients of scurfy lymphocytes. γδ T cells in the TCRα(-/-) recipients of scurfy cells markedly expanded and expressed a highly activated (CD62L(lo)CD44(hi)) phenotype. The activated γδ T cells expressed high levels of CD39 and NKG2D on their cell surface. A high frequency of scurfy T cells in TCRα(-/-) recipients produced IL-10, suggesting that γδ T cells may enhance suppressor cytokine production from scurfy T cells in TCRα(-/-) recipients. This study indicates that γδ T cells may contribute to the maintenance of immunological homeostasis by suppressing autoreactive T cells in liver and lung.

Topics: Adoptive Transfer; Animals; Antigens, CD; Apyrase; Autoimmune Diseases; Autoimmunity; Dermatitis; Forkhead Transcription Factors; Hepatitis; Homeostasis; Interleukin-10; Liver; Lung; Lymphocyte Activation; Mice, Inbred C57BL; NK Cell Lectin-Like Receptor Subfamily K; Pneumonia; Receptors, Antigen, T-Cell, alpha-beta; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocytes, Regulatory

In airways, the ecto-nucleoside triphosphate diphosphohydrolase CD39 plays a central role in the regulation of physiological mucosal nucleotide concentrations and likely contributes to the control of inflammation because accelerated ATP metabolism occurs in chronic inflammatory lung diseases. We sought to determine whether constant elevated CD39 activity in lung epithelia is sufficient to cause inflammation and whether this affects the response to acute LPS or Pseudomonas aeruginosa exposure. We generated transgenic mice overexpressing human CD39 under the control of the airway-specific Clara cell 10-kDa protein gene promoter. Transgenic mice did not develop any spontaneous lung inflammation. However, intratracheal instillation of LPS resulted in accelerated recruitment of neutrophils to the airways of transgenic mice. Macrophage clearance was delayed, and the amounts of CD8(+) T and B cells were augmented. Increased levels of keratinocyte chemoattractant, IL-6, and RANTES were produced in transgenic lungs. Similarly, higher numbers of neutrophils and macrophages were found in the lungs of transgenic mice infected with P. aeruginosa, which correlated with improved bacteria clearance. The transgenic phenotype was partially and differentially restored by coinstillation of P2X(1) or P2X(7) receptor antagonists or of caffeine with LPS. Thus, a chronic increase of epithelial CD39 expression and activity promotes airway inflammation in response to bacterial challenge by enhancing P1 and P2 receptor activation.

Topics: Animals; Antigens, CD; Apyrase; Bacterial Infections; Chromatography, High Pressure Liquid; Humans; Immunohistochemistry; Mice; Mice, Transgenic; Pneumonia; Real-Time Polymerase Chain Reaction; Respiratory Mucosa; Reverse Transcriptase Polymerase Chain Reaction

Influenza virus is a worldwide health problem with significant economic consequences. To study the gene expression pattern induced by influenza virus infection, it is useful to reveal the pathogenesis of influenza virus infection; but this has not been well examined, especially in vivo study.. To assess the influence of influenza virus infection on gene expression in mice, mRNA levels in the lung and tracheal tissue 48 h after infection were investigated by cDNA array analysis.. Four-week-old outbred, specific pathogen free strain, ICR female mice were infected by intra-nasal inoculation of a virus solution under ether anesthesia. The mice were sacrificed 48 h after infection and the tracheas and lungs were removed. To determine gene expression, the membrane-based microtechnique with an Atlas cDNA expression array (mouse 1.2 array II) was performed in accordance with the manual provided.. We focused on the expression of 46 mRNAs for cell surface antigens. Of these 46 mRNAs that we examined, four (CD1d2 antigen, CD39 antigen-like 1, CD39 antigen-like 3, CD68 antigen) were up-regulated and one (CD36 antigen) was down-regulated. Although further studies are required, these data suggest that these molecules play an important role in influenza virus infection, especially the phase before specific immunity.

Topics: Adenosine Triphosphatases; Animals; Antigens, CD; Antigens, CD1; Antigens, CD1d; Antigens, Differentiation, Myelomonocytic; Antigens, Surface; Apyrase; Chick Embryo; Down-Regulation; Female; Gene Expression; Mice; Mice, Inbred ICR; Oligonucleotide Array Sequence Analysis; Orthomyxoviridae Infections; Pneumonia; RNA, Messenger; Up-Regulation