MAST CELL HETEROGENEITY IN RAT LUNGS IN A MODEL OF FAT EMBOLISM AFTER TREATMENT WITH DRUGS RELATED TO THE RENIN ANGIOTENSIN SYSTEM
Authors: Siddiqi Ahsan , Siddiqi Saba , Arif Dauod , Haferkamp Thomas , Lind Taylor , Poisner Alan , Pour Mohammad , Monaghan Paula , Hamidpour Soheila , Molteni Agostino 
Published: June 2021

IntroductionMast cell inhibition reduces the inflammation and vascular remodeling of pulmonary hypertension (1). In a rat model of fat embolism (FE) induced by iv triolein (T), pulmonary arterial vasculitis, hypertension, inflammation and fibrosis developed within 48 hours (2) and these were prevented by drugs interfering with the renin‐angiotensin system (RAS) such as captopril, losartan and the renin inhibitor aliskiren (3–4). Aliskiren also reduced the mast cell number markedly increased by T (5). Since mast cells are of different size, shape and organ location, we examined their presence in lungs of T‐treated rats and the influence of the three RAS modifying drugs.MethodsSprague Dawley rats (280–300 g) were dosed iv with 0.2 ml T (n=17) or saline (n=7). One hour later 0.2 ml of saline (n=17), aliskiren (50 mg/kg n=6 or 100 mg/kg n=6), captopril (50 mg/kg n=6) or losartan (10 mg/kg n=6) were given ip to the various groups. The saline treated rats received 0.2 ml saline ip one hour later. All rats were necropsied 48 hours later under isofluorane anesthesia. Lungs were fixed in 10% formalin and Hematoxylin and Eosin stained for morphology, trichrome for fibrosis and CD 117 for mast cells. A pathologist unaware of the slides' identity took 10 random photographs at 400× for each slide. The camera used for the photograph was not the one used for our previous studies but our recently acquired with better resolution power. Mast cells were counted by 3 counters also unaware of the slides' identity.ResultsAs reported T injection induced pulmonary vasculitis, septal inflammation and fibrosis markedly reduced by aliskiren, captopril and losartan. Most of the mast cells had small, oval, intensively stained cytoplasm and nucleus. Others had less intensively stained cytoplasm and nucleus, both large and not so compact as those ones of the small mast cells. Both small and large cells' location was in the adventitia, the thickened septa and subpleural space. Contrarily to our previous observations, mast cells both small and large were seen in similar numbers in controls, T+saline, T+losartan and T+captopril while a marked increase was present after the two aliskiren doses (p= 0.002 and 0.03 respectively). The increase was mostly related to the large cells 83% and 90% for aliskiren vs 50% with the other groups. These large cells were not well visualized by the previously used camera and were of difficult identification.ConclusionDifferent size and shape of the mast cells was evidenced by the new camera contradicting our previous observations (5). Renin and prorenin stained cells however show the same pattern in size and shape after these drug treatments (6). Our preliminary data suggests a better evidence, count and evaluation of the mast cells and the possibility of different pharmacological pathways of the three RAS related drugs on their protection of FE induced lung damage.Support or Funding InformationSupported by the Catherine T Geldmacher Foundation, St. Louis, MOThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.