The Analysis of Phagocytic Myeloid Cells in Low and High Fiber Fed Mice after Three Weeks of Hypoxia

Abstract

Pulmonary hypertension (PH) is a devastating disease that is characterized by increased blood pressure (BP) in the pulmonary vasculature. Immune cells participate in adverse cardiovascular remodelling of pulmonary vessels and could represent targets for PH treatment. It has been shown that patients with PH have increased numbers of interstitial macrophages and dendritic cells in the lungs that originate from circulating immune cells. These myeloid immune cells migrate to the vessel wall and promote vascular hypertrophy. Attenuation of immune cell invasion into the vessel wall could potentially slow the progression of PH. One of the possible ways to reduce inflammation in the cardiovascular system is dietary modification with increased content of soluble fiber. Soluble fiber increases the level of short chain fatty acids (SCFAs) in the plasma which demonstrate anti‐inflammatory properties in systemic hypertension and cardiac overload. In different models of cardiovascular diseases high fiber (HFi) diet and SCFAs improve cardiovascular functions reducing the level of immune cells at the site of injury. The effects of HFi diet on the pulmonary circulation are unknown. This study establishes the effects of low (LFi) and HFi diet on macrophage and dendritic cell composition in the lungs in the model of hypoxia‐induced PH.C57bl/6j mice were fed with LFi and HFi diet five weeks before and three weeks during hypoxic exposure (10% O2). After that hematocrit, cecum, spleen and body weight were measured. Flow cytometry was used to identify the proportion of alveolar and interstitial macrophages and dendritic cells in the lungs.Hypoxic animals had increased hematocrit level compared to normoxic controls. Hematocrit did not differ between LFi fed animals and HFi fed animals in hypoxic conditions but in normoxia hematocrit was higher in LFi diet group. Cecum weight was significantly higher in HFi fed mice than in LFi fed mice whereas total body weight and spleen weight was not affected by diet composition. The percentage of alveolar macrophages (CD11b+CD11c+CD64+) did not differ between groups. Hypoxia increased the proportion of dendritic cells (CD11b+MHCll+CD24+) and reduced the proportion of interstitial macrophages (CD11b+MHCll+CD64+) among CD11b+MHC ll+ cells. Dietary fiber did not affect the proportion of dendritic cells and interstitial macrophages in normoxic and hypoxic animals.This data demonstrates that three weeks of hypoxia changes the proportion of CD11b+ dendritic cells and interstitial macrophages in the mouse lungs however soluble dietary fiber did not affect it.