title: Lung mast cells are a source of secreted phospholipases A2.
abstract: BACKGROUND
  Secreted phospholipases A(2) (sPLA(2)s) are released in plasma and other biologic fluids of patients with inflammatory, autoimmune, and allergic diseases.
  
  
  OBJECTIVE
  We sought to evaluate sPLA(2) activity in the bronchoalveolar lavage fluid (BALF) of asthmatic patients and to examine the expression and release of sPLA(2)s from primary human lung mast cells (HLMCs).
  
  
  METHODS
  sPLA(2) activity was measured in BALF and supernatants of either unstimulated or anti-IgE-activated HLMCs as hydrolysis of oleic acid from radiolabeled Escherichia coli membranes. Expression of sPLA(2)s was examined by using RT-PCR. The release of cysteinyl leukotriene (LT) C(4) was measured by means of enzyme immunoassay.
  
  
  RESULTS
  Phospholipase A(2) (PLA(2)) activity was higher in the BALF of asthmatic patients than in the control group. BALF PLA(2) activity was blocked by the sPLA(2) inhibitors dithiothreitol and Me-Indoxam but not by the cytosolic PLA(2) inhibitor AZ-1. HLMCs spontaneously released a PLA(2) activity that was increased on stimulation with anti-IgE. This PLA(2) activity was blocked by dithiothreitol and Me-Indoxam but not by AZ-1. HLMCs constitutively express mRNA for group IB, IIA, IID, IIE, IIF, III, V, X, XIIA, and XIIB sPLA(2)s. Anti-IgE did not modify the expression of sPLA(2)s. The cell-impermeable inhibitor Me-Indoxam significantly reduced (up to 40%) the production of LTC(4) from anti-IgE-stimulated HLMCs.
  
  
  CONCLUSIONS
  sPLA(2) activity is increased in the airways of asthmatic patients. HLMCs express multiple sPLA(2)s and release 1 or more of them when activated by anti-IgE. The sPLA(2)s released by mast cells contribute to LTC(4) production by acting in an autocrine fashion. Mast cells can be a source of sPLA(2)s in the airways of asthmatic patients.
authors.affiliation: Department of Clinical Immunology and Allergy and the Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy. triggian@unina.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Triggiani
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giannattasio
authors.forename: Cecilia
authors.initials: C
authors.lastname: Calabrese
authors.forename: Stefania
authors.initials: S
authors.lastname: Loffredo
authors.forename: Francescopaolo
authors.initials: F
authors.lastname: Granata
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fiorello
authors.forename: Mario
authors.initials: M
authors.lastname: Santini
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.forename: Gianni
authors.initials: G
authors.lastname: Marone
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001249:Asthma / Q000276:immunology*; D001388:Aziridines / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002219:Carbamates / Q000494:pharmacology; D002478:Cells, Cultured; D004229:Dithiothreitol / Q000494:pharmacology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007212:Indolizines / Q000494:pharmacology; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology*; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D009285:Naphthoquinones / Q000494:pharmacology; D054497:Phospholipases A2, Secretory / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C507359:2-aziridin-1-yl-3-((2-((2-(3-aziridin-1-yl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)thio)ethoxy)ethyl)thio)naphthoquinone; D000888:Antibodies, Anti-Idiotypic; D001388:Aziridines; D002219:Carbamates; D007212:Indolizines; D009285:Naphthoquinones; C026408:anti-IgE antibodies; C119389:indoxam; D017997:Leukotriene C4; D007073:Immunoglobulin E; D054497:Phospholipases A2, Secretory; D004229:Dithiothreitol