Involvement of peptidoleukotrienes in antigen-dependent thromboxane (TX) synthesis in IgG1-sensitized guinea pig lungs.
Lungs from IgG1-sensitized guinea pigs synthesize both leukotrienes (LTs) and thromboxane (Tx) upon ex vivo antigen challenge. This study was undertaken to investigate whether antigen-dependent Tx synthesis could result from prior formation of LTD4. In IgG1-sensitized lungs, LTD4 effectively induced Tx formation (ED50 = 2-4 nM). In these lungs, the levels of antigen-dependent formation of LTD4 (8-26 nM formed by 0.01-10 micrograms/ml antigen challenge) were 2-7 X greater than the ED50 value of LTD4-stimulated Tx synthesis. In addition, incubation of the sensitized lungs with ICI-198,615, a LTD4 antagonist, prior to antigen-challenge prevented Tx formation (IC50 = 0.01 microM). Our results indicate that LTD4 generated from IgG1-sensitized lungs could play a prominent role in stimulating Tx synthesis. LTC4 may also be involved because of rapid formation of LTC4 upon antigen-stimulation and its capacity to induce Tx synthesis.
Cheng
J B
JB
Department of Immunology and Infectious Diseases, Pfizer Inc., Groton, CT 06340.
Pillar
J
J
Conklyn
M
M
Breslow
R
R
Shirley
J
J
Showell
H J
HJ
D000818:Animals; D006168:Guinea Pigs; D006632:Histamine / Q000096:biosynthesis; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007700:Kinetics; D015289:Leukotrienes / Q000502:physiology*; D008168:Lung / Q000276:immunology*; D011971:Receptors, Immunologic / Q000378:metabolism; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D007074:Immunoglobulin G; D015289:Leukotrienes; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A; D013931:Thromboxanes; D006632:Histamine