Strain-dependency of leukotriene C4 generation from isolated lungs of immunized mice.
1. The antigen-induced leukotriene C4 (LTC4)-like-material release from isolated perfused lungs of actively sensitized Swiss, Balb/C and CBA/J mice was compared. The intra-tracheal (i.t.) instillation of 1 and 100 micrograms ovalbumin to lungs from Swiss mice was followed by a dose-dependent generation of LTC4-like material into the effluent, as detected by radio-immunoassay and h.p.l.c., followed by an enzyme-immunoassay. In contrast, lungs from sensitized Balb/C and CBA/J mice failed to exhibit LTC4-like-material release in amounts above the basal values. No histamine secretion was observed when lungs of the three strains of mice were challenged with ovalbumin. 2. The i.t. instillation of 1 or 10 micrograms platelet-activating factor (PAF) or of 100 micrograms arachidonic acid to lungs from non-sensitized mice, induced the release of comparable amounts of LTC4-like-material in the effluent, irrespective to the strain. However, N-formyl-L-methionyl-L-leucyl-L- phenylalanine (fMLP, 0.1, 10 micrograms), was more effective in inducing the release of LTC4-like-material from lung from Swiss and CBA, than from Balb/C, mice. 3. The intraplantar injection of 0.01 microgram ovalbumin to sensitized Swiss mice induced an intense oedema formation, as measured plethysmographically, while Balb/C mice required a dose of antigen at least 10 fold higher for a similar response. CBA/J mice did not respond to antigen challenge in terms of oedema formation. The intraplantar injection of PAF or fMLP to non-immunized mice induced an oedema of similar intensity in all the strains considered. Accordingly, the different responses to ovalbumin of the three strains of mice is not accounted for by different paw responsiveness to inflammatory mediators.4. Swiss and CBA/J mice exhibited higher titers of circulating IgG antibodies, as measured by passive cutaneous anaphylaxis (PCA), than Balb/C mice. Conversely, lower IgE titers were measured in the serum of sensitized Swiss and CBA/J mice, as compared to Balb/C.5. Our results demonstrate a strain-dependency of antigen-induced LTC4 release from lungs from sensitized mice. This difference is related to the ability of sensitized animals to develop immediate hypersensitivity responses, such as paw oedema formation, but not to the antibody subclass involved in the immunization. Strain-dependent factors may influence the intensity of the response to antigen stimulation. It is thus essential to characterize the different components of the immune response when mouse models for studying hypersensitivity reactions are developed.
Zuany-Amorim
C
C
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur, INSERM No. 285, Paris, France.
Vargaftig
B B
BB
Maclouf
J
J
Pretolani
M
M
D000818:Animals; D000906:Antibodies / Q000097:blood; D000941:Antigens / Q000276:immunology*; D016718:Arachidonic Acid / Q000494:pharmacology; D006636:Histamine Release; D007114:Immunization; D017997:Leukotriene C4 / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010477:Perfusion; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D000906:Antibodies; D000941:Antigens; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D017997:Leukotriene C4; D009240:N-Formylmethionine Leucyl-Phenylalanine