Gene expression signatures in neutrophils exposed to glucocorticoids: A new paradigm to help explain “neutrophil dysfunction” in parturient dairy cows

Invited review: Relationship between cattle transport, immunity and respiratory disease

“…Differentially expressed genes fell into three major functional groups: immune function, apoptosis and wound healing. These expression changes largely correlated with the neutrophil count profile (Table 1), which relates to blood cortisol concentration in numerous models of bovine stress (Burton et al, 2005;Weber et al, 2006;Buckham Sporer et al, 2008). To our knowledge, this is the first study (Buckham Sporer et al, 2008) that has reported transportation-induced changes in the expression of key neutrophil inflammatory and antibacterial genes in association with peak cortisol and neutrophilia stress responses.…”

“…Reduction of this adhesion molecule from the surface of neutrophils, where it is constitutively expressed on resting cells before activation, suggests that weaning may have had a negative impact on the ability of these cells to roll along and adhere to the endothelium lining of vessels and thus, more cells remained in circulation as evidenced by neutrophilia (Lynch et al, 2012). This phenomenon has been documented in stressed cattle, most notably coinciding with parturition (Burton et al, 2005) and following transportation (Yagi et al, 2004).…”

“…Gene expression regulation results from the binding of cortisol to its GR in the cytoplasm of target cells, with subsequent translocation of hormone-activated receptors into the nucleus and modulation of gene transcription by direct (receptor-DNA) and indirect (receptor-protein-DNA) interactions in regulatory regions of cortisol-sensitive genes (Preisler et al, 2000;Weber et al, 2006). In addition, bovine neutrophils have been shown to exhibit differential expression of genes important to roles of immune function, apoptosis, tissue remodelling, and various metabolic and cellular functions in response to glucocorticoids in vitro and in vivo (Burton et al, 2005). Findings from these studies have implicated the downregulation of L-selectin as an important factor mediating neutrophilia (Burton et al, 2005).…”

“…In addition, bovine neutrophils have been shown to exhibit differential expression of genes important to roles of immune function, apoptosis, tissue remodelling, and various metabolic and cellular functions in response to glucocorticoids in vitro and in vivo (Burton et al, 2005). Findings from these studies have implicated the downregulation of L-selectin as an important factor mediating neutrophilia (Burton et al, 2005). More recently, Lynch et al (2012) reported that neutrophil surveillance and phagocytic activity were affected by weaning in beef calves; however, bactericidal activity was unaffected.…”

“…The genes selected for profiling were sensitive to glucocorticoids in other stress models (Burton et al, 2005;Weber et al, 2006) and included Fas, A1, MMP-9, L-selectin, bactericidal/permeability-increasing protein (BPI ), transforming growth factor-β receptor type III (subsequently referred to as β-glycan), and GRα. In all, 88 genes were found to be differentially expressed between −24 and 4.5, 9.75 or 14.25 h relative to transport, when cortisol and neutrophilia were at their peaks.…”