Mast Cells and Macrophages of Rats lungs in an Acute Model of Fat Embolism

Abstract

IntroductionFat embolism (FE) by IV injection of Triolein (T) causes vasculitis, septal inflammation and fibrosis in rat lungs at 48 hours, which is mitigated by two drugs acting on the renin‐angiotensin system (RAS) Captopril and Losartan. An increase in mast cells is noted following administration of T, with an even higher increase by concomitant treatment with Captopril and significant induction by Losartan. This study examines the presence and number of macrophages in rat lungs after T treatment with or without addition of Captopril and Losartan.MethodsSprague‐dawley rats (280–300g) were treated with 0.2 ml IV T or saline. One hour later 0.2 ml of Saline, Captopril, or losartan was administered IP in the 3 T subgroups. All rats were necropsied 48 hours later under isoflurane anesthesia. Lungs were fixed in 10% formalin and stained with: 1. hematoxylin eosin for morphology, 2. trichrome for fibrosis, 3. CD 117 for mast cells and 4. CD 68 for macrophages. Two pathologists unaware of slide identity reviewed ten random photographs of all slides at 400x for macrophage count and histopathological evaluation. Slide photographs and mast cell count was performed by 2 other pathologists.ResultsAs previously reported, T injection induced pulmonary vasculitis, septal inflammation and fibrosis which was markedly reduced by the RAS inhibitors Captopril and Losartan. Contrary to the statistically significant increase of mast cells after these 3 treatments, macrophage counts were only increased but minimally by T and T + Captopril. T + Losartan administration yielded a macrophages count similar to that of the saline controls.Two types of macrophages were observed: one composed of small cells with compact cytoplasm and nucleus, similar in their size to the size of the mast cells and a second type with a larger vacuolated cytoplasm. The number of cells of this second group was rather small, so that any increase of these cells could not influence the macrophages total number.ConclusionBoth mast cells and macrophages play a determinant role in the pathogenesis of the inflammatory and fibrotic pulmonary damage after T fat embolism. A different response to the injury was observed between the numbers of these two series of cells in the earlier phase of the injuries. The difference also observed in mast cells versus macrophages number present following T + Captopril and T + Losartan administration, suggesting a diversely regulated pharmacologic activity of the Renin Angiotensin System of the two drugs in the protection of the fat embolism mediated damage.Support or Funding InformationFunded and supported by the Catherine T. Geldmacher Foundation St. Louis, Missouri.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.