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Blockade of eosinophil migration and airway hyperresponsiveness by cPLA2-inhibition

Nature Immunology volume 2, pages 145–149 (2001)Cite this article

Abstract

We examined the role of a cytosolic phospholipase A2 (cPLA2) in antigen-induced eosinophil infiltration of airways and in airway hyperresponsiveness to methacholine. Inhibition of cPLA2, or blockade of the platelet-activating factor (PAF) receptor, blocked antigen-induced airway hyperresponsiveness and suppressed eosinophil infiltration. Neither cyclooxygenase nor 5-lipoxygenase inhibition had either effect. We show here that, in antigen-sensitized guinea pigs, cPLA2 inhibition prevents both eosinophilic infiltration and subsequent airway hyperresponsiveness after antigen challenge. We also show that this effect is mediated by first-step hydrolysis of membrane phospholipid into lysophospholipid rather than by prostanoid or leukotriene metabolites of arachidonate.

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Figure 1: Effects of TFMK, indomethacin and AA-861, E6123 and ebastine on antigen-induced early-phase airway obstruction in guinea pigs.
Figure 2
Figure 3: Effects of TFMK, indomethacin and AA-861, E6123 and ebastine on bronchial hyperresponsiveness to methacholine 24 h after antigen inhalation in guinea pigs.
Figure 4: Time course of the OVA-induced change in BAL inflammatory cell numbers.
Figure 5: Effects of TFMK, indomethacin and AA-861, E6123 and ebastine on eosinophil and neutrophil accumulation in BAL fluid 24 h after antigen inhalation in guinea pigs.
Figure 6: Airway sections 24 h after antigen challenge.
Figure 7: Effects of TFMK and E6123 on eosinophil accumulation in BAL fluid 24 h after intranasal administration of IL-5 in guinea pigs.
Figure 8: Effects of TFMK on FMLP-CB–induced TXB2 production.

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Acknowledgements

This work was supported by NHLBI grant RO1-HL46368 and by NHLBI SCOR grant HL-56399. S. M. and H. S. were supported by the AstraZeneca Traveling Fellowship

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Authors and Affiliations

  1. Third Department of Internal Medicine, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa, Japan

    Shigeharu Myou, Masaki Fujimura, Kazuyoshi Kurashima, Toshiyuki Kita & Shinji Nakao

  2. Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, Chicago, 60637, IL, USA

    Hiroyuki Sano, Xiangdong Zhu, Takanobu Shioya, Nilda M. Munoz & Alan R. Leff

  3. Pathology Section, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa, Japan

    Akitaka Nonomura

  4. Department of Chemistry, University of Illinois at Chicago, Chicago, IL, USA

    Kwang Pyo Kim & Wonhwa Cho

  5. Department of Neurobiology, Pharmacology and Physiology and Committee of Clinical Pharmacology and Cell Physiology, The University of Chicago, USA

    Alan R. Leff

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Correspondence to Alan R. Leff.

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Myou, S., Sano, H., Fujimura, M. et al. Blockade of eosinophil migration and airway hyperresponsiveness by cPLA2-inhibition. Nat Immunol 2, 145–149 (2001). https://doi.org/10.1038/84244

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