Mast cell histamine mediates intestinal immune response to early life stress in piglets via histamine 1 receptor (H1R)

Abstract

Abstract Mast cells are important immune modulators of stress-related gastrointestinal (GI) disorders. Our previous studies investigating early life stress in piglets showed that histamine, a major mast cell granule mediator is released within minutes of early weaning stress and is followed by increased intestinal mucosal expression of histamine receptor subtypes. The precise contribution of histamine to stress-induced GI immune responses is unknown. The objective of this study was to test the hypothesis that stress-induced intestinal immune response is mediated through the histamine 1 receptor (H1R). Fifteen-day-old female Yorkshire piglets were administered either saline vehicle or the H1R antagonist, desloratadine (2 mg/kg; intramuscular), 30 minutes prior to early weaning stress. At weaning, piglets were weaned from their dams and housed in nursery pens with ad libitum access to water. At 24 hours post-weaning, mid-jejunum and mesenteric lymph nodes (MLN) were collected for subsequent qPCR gene expression as well as IHC localization and protein expression analyses. Unweaned control piglets remained with the sow and were collected immediately at weaning. Gene expression for H1R was not influenced by weaning; however, immunohistochemical analysis of H1R revealed increased expression and localization in lamina propria cells and myofibroblasts in jejunal villi and expression in the longitudinal and circular muscle layers in early weaned piglets. In the MLN, weaning increased the expression of TNFα, TGFβ, and β-Integrin. This response was reduced in the group treated with the H1R antagonist. Together, these data demonstrate that histamine via H1R plays an important role in early weaning stress-induced intestinal immune responses.