title: Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure.
abstract: Hypertension (HTN) is a prevalent condition with complex etiology and pathophysiology. Evidence exists of significant communication between the nervous system and the immune system (IS), and there appears to be a direct role for inflammatory bone marrow (BM) cells in the pathophysiology of hypertension. However, the molecular and neural mechanisms underlying this interaction have not been characterized. Here, we transplanted whole BM cells from the beta 1 and 2 adrenergic receptor (AdrB1(tm1Bkk)AdrB2(tm1Bkk)/J) knockout (KO) mice into near lethally irradiated C57BL/6J mice to generate a BM AdrB1.B2 KO chimera. This allowed us to evaluate the role of the BM beta 1 and beta 2 adrenergic receptors in mediating BM IS homeostasis and regulating blood pressure (BP) in an otherwise intact physiological setting. Fluorescence-activated cell sorting demonstrated that a decrease in systolic and mean BP in the AdrB1.B2 KO chimera is associated with a decrease in circulating inflammatory T cells, macrophage/monocytes, and neutrophils. Transcriptomics in the BM identified 7,419 differentially expressed transcripts between the C57 and AdrB1.B2 KO chimera. Pathway analysis revealed differentially expressed transcripts related to several cell processes in the BM of C57 compared with AdrB1.B2 KO chimera, including processes related to immunity (e.g., T-cell activation, T-cell recruitment, cytokine production, leukocyte migration and function), the cardiovascular system (e.g., blood vessel development, peripheral nerve blood flow), and the brain (e.g., central nervous system development, neurite development) among others. This study generates new insight into the molecular events that underlie the interaction between the sympathetic drive and IS in modulation of BP.
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida;
authors.forename: Niousha
authors.initials: N
authors.lastname: Ahmari
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida;
authors.forename: Jordan T
authors.initials: JT
authors.lastname: Schmidt
authors.affiliation: Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, Florida; and.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Krane
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida;
authors.forename: Wendi
authors.initials: W
authors.lastname: Malphurs
authors.affiliation: Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Cunningham
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida;
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Owen
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida;
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Martyniuk
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida; jasenkaz@ufl.edu.
authors.forename: Jasenka
authors.initials: J
authors.lastname: Zubcevic
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods; D004195:Disease Models, Animal; D053263:Gene Regulatory Networks / Q000235:genetics*; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2
keywords: adrenergic receptors; bone marrow; chimera; immune system; sympathetic drive