ΔdblGATA mice were purchased from Jackson Laboratory (033551). Male hemizygote mice (ΔdblGATA/Y) and female heterozygote mice (ΔdblGATA/+) were maintained in a C57BL/6 genetic background to generate wild-type (WT) (+/Y) and knockout (KO) (ΔdblGATA/Y) littermates. C57BL/6 mice and Sprague Dawley rats were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. Animals were randomly assigned to various treatment groups for each experiment. Mice or rats were maintained on a 12-h light–dark cycle with a regular unrestricted diet. To establish a SuHx-induced PH mouse model, 8–10-week-old male or female mice received weekly subcutaneous injections of SU5416 (20 mg·kg−1; S8442, Sigma Aldrich) for 3 weeks and were housed in an airtight plexiglass chamber (China Innovation Instrument) with 10% O2 [27 (link)]. To establish a SuHx-induced PH rat model, 200 g male rats received a single SU5416 injection (20 mg·kg−1) and were then housed in 10% O2 for 3 weeks. For the EOS depletion mouse model, the anti-IL5-neutralising antibody TRFK5 (554391, BD Pharmingen) was administrated at a dose of 2 μg per mouse each week, with a total of three doses for each mouse, through intravenous injection [28 (link)]. Sex- and age-matched littermates injected with an equal dose of isotype control antibody (IgG1κ; 559072, BD Pharmingen) were used as controls. For the EOS-depletion rat model, the anti-IL5-neutralising antibody TRFK5 (14-7052-85, Invitrogen) was administrated at a dose of 17.5 μg per rat each week, three doses for each rat, and isotype control antibody was injected at an equal volume. For N-formyl peptide receptor 2 (FPR2) agonist Ac2-26 (HY-P1098A, MCE) treatment, mice were intraperitoneally injected at a dose of 50 μg per mouse every 3 days. The control mice were injected with an equal volume of vehicle. All animal experiments were conducted under the approval of the Animal Research Committee of the Institute of Laboratory Animals, Chinese Academy of Medical Sciences, and Peking Union Medical College (ACUC-A01-2020-017).
Additional materials and methods are available in thesupplementary material .
Additional materials and methods are available in the
