Lipopolysaccharide from Escherichia coli reduces antigen-induced bronchoconstriction in actively sensitized guinea pigs.
Bronchoconstriction (BC) is the main feature of anaphylaxis in the guinea pig. Since LPS induces lung inflammation and antigen-induced BC depends on the endogenous formation of histamine and arachidonate metabolites, we studied whether LPS might modulate antigen-induced BC. Guinea pigs were sensitized subcutaneously with 10 micrograms ovalbumin (OA) on days 0 and 14. LPS (100 micrograms/kg) was injected intravenously on day 21, and daily injections of LPS were continued before the antigenic challenge on day 22, 23, 24, or 25. Intratracheal injection of 100 micrograms OA induced an abrupt and reversible BC. Single or repetitive injections of LPS reduced BC. LPS is likely to reduce the OA-induced BC by affecting the histamine-dependent component of BC, since (a) LPS induced a partial degranulation of lung mast cells; (b) BC is reduced by mepyramine, an histamine receptor antagonist; (c) LPS did not affect BC in mepyramine-treated guinea pigs; (d) LPS reduced histamine release by OA-stimulated guinea pig lungs in vitro. Moreover, the in vitro OA-induced production of arachidonate metabolites was also reduced by LPS. The decreased formation of TXB2 was not only secondary to a reduced release of histamine, since LPS inhibited TXB2 formation in the presence of mepyramine. Finally, the FMLP-induced BC and mediator release were inhibited by LPS, whereas the platelet activating factor-induced pulmonary responses were not. Thus, the protective effect of LPS is not antigen-specific and does not result from a general desensitization. These studies indicate that a single dose of LPS reduces the antigen-induced BC by reducing histamine release from lung mast cells, although a decreased formation of eicosanoids may contribute to the protective effect of LPS.
Vannier
E
E
Unité de Pharmacologie Cellulaire, Institut Pasteur, Paris, France.
Lefort
J
J
Lellouch-Tubiana
A
A
Terlain
B
B
Vargaftig
B B
BB
D000818:Animals; D000941:Antigens / Q000276:immunology; D001241:Aspirin / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects* / Q000276:immunology; D015550:Cell Degranulation / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D006632:Histamine / Q000378:metabolism; D006967:Hypersensitivity / Q000503:physiopathology*; D007970:Leukopenia / Q000139:chemically induced; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008407:Mast Cells / Q000648:ultrastructure; D008854:Microscopy, Electron; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism
D000941:Antigens; D004731:Endotoxins; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D013929:Thromboxane B2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006632:Histamine; D010047:Ovalbumin; D011738:Pyrilamine; D001241:Aspirin