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ABSENCE OF MAST CELLS IN AN EXPERIMENTAL MODEL OF PULMONARY AND CARDIAC FIBROSIS, THE CUX‐1 MICE
Author(s) -
Reddy Navya A.,
Raza Farhan,
Said Ahmed,
Livingston Safia,
Jacobsen David,
Kearns Donovan,
Baybutt Richard,
Van Den Heuvel Gregory,
Molteni Agostino,
Hamidpour Soheila
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.50.10
Subject(s) - fibrosis , medicine , cardiac fibrosis , pulmonary fibrosis , pathology , lung , masson's trichrome stain , angiotensin ii , endocrinology , receptor
Both pulmonary and cardiovascular (CV) fibrosis have a significant role in clinical medicine, however the pathophysiology of fibrosis in these organs is poorly understood (1). Previous rat models of pulmonary fibrosis have shown increased staining of renin and mast cells (MC) production in pulmonary tissue following injection with Triolein (T), a substance comprising 80% of human fat and which is experimentally used to induce fat embolism (FE) (2). MCs are known to produce renin in injured pulmonary tissue, leading to Angiotensin II mediated fibroblasts proliferation (3). The angiotensin II receptor blocker losartan is associated with reduced MCs in fibrotic lungs and a reduction of fibroblasts proliferation, also suggesting that MCs may have a significant correlation with the fibrosis (4). We aimed to identify one of the mechanisms of CV fibrosis by determining if MC could be found within the lung and cardiac tissue of CUX 1 (CUT‐like homeobox) transgenic mice. Although the CUX‐1 gene is present in all metazoans, its constitutive expression such as in polycystic kidneys blocks cyclin dependent kinase inhibitors p21 and p27, leading to hepatic, pulmonary and cardiac fibrosis (5). Previous studies of CUX‐1 mice have shown severe inflammation of the pulmonary and coronary arteries with media thickening, luminal patency reduction, adventitial fibrosis and MCs presence (5). In our study, 6 wild type and 6 CUX‐1 transgenic mice were sacrificed by isoflurane anesthesia and necropsied. Lungs and heart were collected, fixed in 10% formalin and stained with H & E (morphometric scoring), Trichrome (fibrosis), May‐Grünwald‐Giemsa and CP‐11‐C‐kit (MCs). In each organ slide, 10 photographs were taken at random at 400× magnification by 2 pathologists unaware of the slide identity who also reviewed the slides (5). Mild lung and CV inflammation and fibrosis were observed in wild type mice while the CUX‐1 mice presented with very severe fibrosis, particularly in the bronchial basal membrane, the peribronchial pulmonary arteries and the coronary arteries. May‐Grünwald‐Giemsa staining showed very few MCs in the heart of wild type mice and none in the CUX‐1. MCD staining did not show MCs in either organs, not withstanding the severe damage. It remains to be seen whether the lack of MCs, as seen in this experimental model, has a pathogenetic role in the development of pulmonary and cardiac fibrosis. Further mechanisms of fibrotic damage should be explored to identify potential therapeutic options in patients with significant fibrotic conditions. Support or Funding Information Wheaton College Research Fund