Asthma ; pathology ; Basophils ; physiology ; Bronchi ; pathology ; Humans ; Neutrophils ; physiology

Prostaglandin D2 (PGD2) is a major prostanoid, produced mainly by mast cells, in allergic diseases, including bronchial asthma. PGD2-induced vasodilatation and increased permeability are well-known classical effects that may be involved in allergic inflammation. Recently, novel functions of PGD2 have been identified. To date, D prostanoid receptor (DP) and chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) have been shown to be major PGD2-related receptors. These two receptors have pivotal roles mediating allergic diseases by regulating the functions of various cell types, such as TH2 cells, eosinophils, basophils, mast cells, dendritic cells, and epithelial cells. This review will focus on the current understanding of the roles of PGD2 and its metabolites in TH2 inflammation and the pathogenesis of bronchial asthma.
Asthma/*etiology/immunology ; Basophils/physiology ; Eosinophils/physiology ; Humans ; Mast Cells/physiology ; Prostaglandin D2/*physiology ; Receptors, Immunologic/physiology ; Receptors, Prostaglandin/physiology ; Th2 Cells/*immunology

OBJECTIVETo observe the effects of Qingkailing injection on RBL-2H3 cell degranulation and histamine release, and discuss the possible mechanism of anaphylactoid reaction induced by Qingkailing injection.

METHODRBL-2H3 cells were incubated with Qingkailing injection for 30 min. Then the morphological changes of cells were observed by transmission electron microscopy. Cell degranulation rate was detected by Alcian blue dye assay, Annexin V binding assay and beta-hexosaminidase assay, and cell histamine release rate was detected by ELISA.

RESULTDifferent concentration of Qingkailing injection can induce the typical morphological changes in RBL-2H3 cell with degranulation. The rates of degranulation and histamine release in Qingkailing injection treated cells were significantly increased and dose-dependent.

CONCLUSIONRBL-2H3 cell degranulation and histamine release can be induced by single administration of Qingkailing injection, and then induced anaphylactoid reaction, which may be one of the possible mechanisms of serious adverse induced by Qingkailing injection for the first administration in clinic.

Animals ; Basophils ; drug effects ; immunology ; physiology ; Cell Degranulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Histamine ; metabolism ; Rats

BACKGROUNDLittle is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles of beta1 and beta2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase (PI3K), src-kinases and extracellular signal regulated kinase (ERK) 1/2 in basophil adhesion and histamine release (HR).

METHODSBasophils (purity of 10% - 50%) were preincubated with anti-CD29 or anti-CD18 blocking antibodies before used for adhesion study. Basophils were preincubated with the pharmacological inhibitors wortmannin, PP1, PD98059 before used for adhesion and HR study. Cell adherence to bovine serum albumin (BSA) or fibronectin (Fn) was monitored using cell associated histamine as a basophil marker and the histamine was measured by the glass fiber assay.

RESULTSBasophil spontaneous adhesion to Fn was inhibited by anti-CD29. Interleukin (IL)-3, granulocyte/macrophage colony stimulating factor (GM-CSF) induced adhesion to BSA was inhibited by anti-CD18. Wortmannin at 1 micromol/L and PP1 at 20 micromol/L strongly interfered with, whereas PD98059 at 50 micromol/L weakly inhibited basophil spontaneous adhesion to Fn. One micromol/L wortmannin strongly inhibited IL-3, IL-5, GM-CSF and anti-IgE induced adhesion to BSA. PP1 at 20 micromol/L partly inhibited anti-IgE induced adhesion. Fifty micromol/L PD98059 marginally inhibited IL-5, weakly inhibited anti-IgE, partly inhibited GM-CSF induced adhesion. Wortmannin, PP1 and PD98059 inhibited anti-IgE (1:100 or 1:1000) induced basophil HR in a dose dependent manner. They inhibited calcium ionophore A23187 (10 micromol/L, 5 micromol/L) induced basophil HR in a dose dependent manner, but to different extend with PP1 being the most efficient.

CONCLUSIONSBasophil spontaneous adhesion to Fn is mediated by beta1-integrins whereas cytokine induced adhesion to BSA is mediated by beta2-integrins. PI3K, src-kinases and ERK1/2 play distinct signaling roles in basophil adhesion and HR. PI3K is the key player while ERK1/2 is the weakest participant.

Androstadienes ; pharmacology ; Antibodies, Anti-Idiotypic ; pharmacology ; Basophils ; physiology ; CD18 Antigens ; physiology ; Cell Adhesion ; Extracellular Signal-Regulated MAP Kinases ; physiology ; Flavonoids ; pharmacology ; Histamine Release ; Humans ; Integrin beta1 ; physiology ; Phosphatidylinositol 3-Kinases ; physiology ; Signal Transduction ; physiology