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Eosinophil chemotaxis induced by several biologically active substances and the effects of apafant on it in vitro.
Arzneimittelforschung. 1997 Oct; 47(10):1112-6.A

Abstract

Chemotaxis of guinea pig eosinophils induced by various stimuli in use of a modified Boyden chamber technique in vitro and the effect of a platelet-activating factor (PAF) antagonist, apafant (CAS 105219-56-5, WEB 2086 BS), on it were examined. The eosinophils were obtained by bronchoalveolar lavage from the animals treated by i.v. injection with Sephadex G-200 and purified by Percoll density gradient centrifugation. PAF significantly and potently induced the chemotaxis at a broad range of 10(-17) to 10(-7) mol/l, where no concentration-dependency was observed. Leukotriene B4 also induced the chemotaxis in a concentration-dependent manner at 10(-14) to 10(-12) mol/l and the enhanced migration was not declined until 10(-7) mol/l. Interleukin-5 (IL-5), IL-8 and regulated on activation normal T expressed and secreted (RANTES) only modestly enhanced the chemotaxis in some concentrations at 10(-13) to 10(-7) mol/l with or without significance and with no concentration-dependency while formyl-methionyl-leucyl-phenylalanine (FMLP), a known chemoattractant, increased the migration at 10(-7) to 10(-5) mol/l. Apafant at 10(-8) to 10(-6) mol/l strongly and concentration-dependently inhibited 10(-8) mol/l PAF-induced chemotaxis. However, the drug showed nominal or no influences on their chemotaxis stimulated by the other agonists, at the concentrations of which the enhanced migration was observed. From these results, it is concluded that IL-5, IL-8 and RANTES, different from PAF and LTB4, are not potent stimuli for the eosinophil chemotaxis and that apafant is a selective antagonist of PAF, which is expected to be therapeutically effective for PAF-associated diseases including bronchial asthma.

Authors+Show Affiliations

Department of Pharmacology, Kyoto Pharmaceutical University, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9368704

Citation

Nabe, T, et al. "Eosinophil Chemotaxis Induced By Several Biologically Active Substances and the Effects of Apafant On It in Vitro." Arzneimittel-Forschung, vol. 47, no. 10, 1997, pp. 1112-6.
Nabe T, Yamamura H, Kohno S. Eosinophil chemotaxis induced by several biologically active substances and the effects of apafant on it in vitro. Arzneimittelforschung. 1997;47(10):1112-6.
Nabe, T., Yamamura, H., & Kohno, S. (1997). Eosinophil chemotaxis induced by several biologically active substances and the effects of apafant on it in vitro. Arzneimittel-Forschung, 47(10), 1112-6.
Nabe T, Yamamura H, Kohno S. Eosinophil Chemotaxis Induced By Several Biologically Active Substances and the Effects of Apafant On It in Vitro. Arzneimittelforschung. 1997;47(10):1112-6. PubMed PMID: 9368704.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Eosinophil chemotaxis induced by several biologically active substances and the effects of apafant on it in vitro. AU - Nabe,T, AU - Yamamura,H, AU - Kohno,S, PY - 1997/11/22/pubmed PY - 1997/11/22/medline PY - 1997/11/22/entrez SP - 1112 EP - 6 JF - Arzneimittel-Forschung JO - Arzneimittelforschung VL - 47 IS - 10 N2 - Chemotaxis of guinea pig eosinophils induced by various stimuli in use of a modified Boyden chamber technique in vitro and the effect of a platelet-activating factor (PAF) antagonist, apafant (CAS 105219-56-5, WEB 2086 BS), on it were examined. The eosinophils were obtained by bronchoalveolar lavage from the animals treated by i.v. injection with Sephadex G-200 and purified by Percoll density gradient centrifugation. PAF significantly and potently induced the chemotaxis at a broad range of 10(-17) to 10(-7) mol/l, where no concentration-dependency was observed. Leukotriene B4 also induced the chemotaxis in a concentration-dependent manner at 10(-14) to 10(-12) mol/l and the enhanced migration was not declined until 10(-7) mol/l. Interleukin-5 (IL-5), IL-8 and regulated on activation normal T expressed and secreted (RANTES) only modestly enhanced the chemotaxis in some concentrations at 10(-13) to 10(-7) mol/l with or without significance and with no concentration-dependency while formyl-methionyl-leucyl-phenylalanine (FMLP), a known chemoattractant, increased the migration at 10(-7) to 10(-5) mol/l. Apafant at 10(-8) to 10(-6) mol/l strongly and concentration-dependently inhibited 10(-8) mol/l PAF-induced chemotaxis. However, the drug showed nominal or no influences on their chemotaxis stimulated by the other agonists, at the concentrations of which the enhanced migration was observed. From these results, it is concluded that IL-5, IL-8 and RANTES, different from PAF and LTB4, are not potent stimuli for the eosinophil chemotaxis and that apafant is a selective antagonist of PAF, which is expected to be therapeutically effective for PAF-associated diseases including bronchial asthma. SN - 0004-4172 UR - https://www.unboundmedicine.com/medline/citation/9368704/Eosinophil_chemotaxis_induced_by_several_biologically_active_substances_and_the_effects_of_apafant_on_it_in_vitro_ L2 - https://medlineplus.gov/bloodthinners.html DB - PRIME DP - Unbound Medicine ER -