prostaglandin-d2 and Bronchitis

Prostaglandin D(2) (PGD(2)), a major prostanoid produced by activated mast cells, has long been implicated in allergic diseases. Recent studies have shown that PGD(2) exerts its effects through two different G-protein-coupled receptors (GPCRs), the D-prostanoid receptor (DP) and the chemoattractant receptor-homologous molecule expressed on T helper type-2 cells (CRTH2), expressed in various human tissues. The PGD(2)/CRTH2 system mediates the chemotaxis of eosinophils, basophils, and Th2 cells, which are involved in the induction of allergic inflammation. We have reported that normal human bronchial epithelial cells (NHBE) and epithelial cell lines (NCI-H(292)) expressed CRTH2, and PGD(2) induces production of IL-8 and GM-CSF. This review discusses the role of CRTH2/DP on epithelial cells and mentions a possible novel receptor for PGD(2).

Topics: Asthma; Bronchi; Bronchitis; Cell Line; Chemotaxis; Epithelial Cells; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-8; MAP Kinase Signaling System; Organ Specificity; Prostaglandin D2; Receptors, Immunologic; Receptors, Prostaglandin; Respiratory Hypersensitivity; RNA, Messenger; Th2 Cells

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Aspirin; Asthma; Bronchitis; Dinoprost; Dinoprostone; Epoprostenol; Humans; Leukotriene B4; Lung; Lung Diseases; Prostaglandin D2; Prostaglandin Endoperoxides, Synthetic; Prostaglandin H2; Prostaglandins D; Prostaglandins E; Prostaglandins F; Prostaglandins G; Prostaglandins H; Pulmonary Circulation; Pulmonary Ventilation; SRS-A

Phospholipases A2 (PLA2) hydrolyzes phospholipids, initiating the production of inflammatory lipid mediators. We have previously shown that in rats, sPLA2 and cPLA2 play opposing roles in the pathophysiology of ovalbumin (OVA)-induced experimental allergic bronchitis (OVA-EAB), an asthma model: Upon disease induction sPLA2 expression and production of the broncho-constricting CysLTs are elevated, whereas cPLA2 expression and the broncho-dilating PGE2 production are suppressed. These were reversed upon disease amelioration by treatment with an sPLA2 inhibitor. However, studies in mice reported the involvement of both sPLA2 and cPLA2 in EAB induction.. To examine the relevance of mouse and rat models to understanding asthma pathophysiology.. OVA-EAB was induced in mice using the same methodology applied in rats. Disease and biochemical markers in mice were compared with those in rats.. As in rats, EAB in mice was associated with increased mRNA of sPLA2, specifically sPLA2gX, in the lungs, and production of the broncho-constricting eicosanoids CysLTs, PGD2 and TBX2 in bronchoalveolar lavage (BAL). In contrast, EAB in mice was associated also with elevated cPLA2 mRNA and PGE2 production. Yet, treatment with an sPLA2 inhibitor ameliorated the EAB concomitantly with reverting the expression of both cPLA2 and sPLA2, and eicosanoid production.. In both mice and rats sPLA2 is pivotal in OVA-induced EAB. Yet, amelioration of asthma markers in mouse models, and human tissues, was observed also upon cPLA2 inhibition. It is plausible that airway conditions, involving multiple cell types and organs, require the combined action of more than one, essential, PLA2s.

Topics: Animals; Arachidonate 5-Lipoxygenase; Arginase; Asthma; Blotting, Western; Bronchitis; Bronchoalveolar Lavage Fluid; Chitinases; Cysteine; Dinoprostone; Disease Models, Animal; Female; Group X Phospholipases A2; Humans; Leukotrienes; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Phospholipases A2, Cytosolic; Phospholipases A2, Secretory; Prostaglandin D2; Rats; Receptors, Leukotriene; Reverse Transcriptase Polymerase Chain Reaction; T-Box Domain Proteins

Human lung mast cells were obtained from pulmonary tissue of normal individuals and patients with chronic bronchitis or emphysema by enzymatic dispersion. Based on their density two mast cell subtypes, a formalin-sensitive (FS) and a formalin-insensitive (FI) cell type, could be separated. Although differences in anti-IgE-induced histamine release could be demonstrated for the mast cell subtypes of normal individuals, these experiments could not be performed for both mast cell subtypes from both patient groups. LTC4 and PGD2 release could be demonstrated for the FS- and FI-mast cell respectively. The release of PGD2 from FI-mast cells of patients with chronic bronchitis was enhanced as compared with normal subjects.

Topics: Aged; Bronchitis; Emphysema; Formaldehyde; Histamine Release; Humans; In Vitro Techniques; Lung; Mast Cells; Middle Aged; Prostaglandin D2; SRS-A