Role of interleukin-5 in enhanced migration of eosinophils from airways of immunized guinea-pigs.
1. Platelet activating factor (PAF), leukotriene B4 (LTB4) and interleukin-5 (IL-5) are potent chemoattractants for guinea-pig eosinophils, which may be involved in eosinophil recruitment and up-regulation in allergic diseases. Eosinophils from the bronchoalveolar lavage fluid (BALF) of ovalbumin-sensitized guinea-pigs were collected 24 h after antigen provocation and migration induced by PAF, LTB4 and rhIL-5 was studied. 2. Total BALF content and distribution of eosinophils were greater in immunized, ovalbumin-challenged guinea-pigs (5.0 +/- 0.8 x 10(6)/guinea-pig; 12 +/- 1%) than in immunized, saline-challenged animals (3.0 +/- 0.7 x 10(6)/guinea-pig; 7 +/- 1%). 3. The chemoattraction of eosinophils isolated on a metrizamide gradient was studied in micro-Boyden chambers, results being expressed as the number of migrating cells (mean +/- s.e. mean). PAF and LTB4-induced migration of eosinophils from immunized and OA-challenged guinea-pigs were significantly enhanced, as compared to immunized and saline-challenged animals (170 +/- 36 vs 35 +/- 9 migrating eosinophils for 10 nM PAF; 271 +/- 60 vs 110 +/- 19 for 1 nM LTB4). 4. The IL-5 antibody TRFK-5, in vivo, reduced eosinophil recruitment in BALF of antigen-challenged immunized animals as well as the enhanced responsiveness of eosinophils from the challenged animals, suggesting a role for IL-5 in the priming of eosinophils in vivo. 5. In contrast to TRFK-5, nedocromil sodium reduced to a similar extent eosinophil, macrophage and lymphocyte recruitment into the BALF of antigen-challenged, but failed to down-regulate the enhanced responsiveness of eosinophils from the challenged animals. 6. The increased eosinophil content in lungs from antigen-challenged guinea-pigs is thus selectively reduced by the anti-IL-5 antibody, which also attenuates the concomitant enhancement of the eosinophil responsiveness, supporting the concept that IL-5 is essential for recruitment and priming of eosinophils in vivo. In contrast, nedocromil sodium reduced non-selectively the total cell recruitment to the airways,but failed to attenuate the enhanced responsiveness of those eosinophils which migrated, indicating that its effects involve a different target.
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM no. 285, Paris, France.
E
E
Coëffier
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D
Joseph
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BB
Vargaftig
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D002465:Cell Movement; D004804:Eosinophils / Q000502:physiology*; D006168:Guinea Pigs; D007114:Immunization; D015848:Interleukin-5 / Q000502:physiology*; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D017835:Nedocromil / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D010972:Platelet Activating Factor / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000941:Antigens; D015848:Interleukin-5; D010972:Platelet Activating Factor; D017835:Nedocromil; D007975:Leukotriene B4; D010047:Ovalbumin