title: Attenuation of monocyte chemotaxis--a novel anti-inflammatory mechanism of action for the cardio-protective hormone B-type natriuretic peptide.
abstract: B-type natriuretic peptide (BNP) is a prognostic and diagnostic marker for heart failure (HF). An anti-inflammatory, cardio-protective role for BNP was proposed. In cardiovascular diseases including pressure overload-induced HF, perivascular inflammation and cardiac fibrosis are, in part, mediated by monocyte chemoattractant protein (MCP)1-driven monocyte migration. We aimed to determine the role of BNP in monocyte motility to MCP1. A functional BNP receptor, natriuretic peptide receptor-A (NPRA) was identified in human monocytes. BNP treatment inhibited MCP1-induced THP1 (monocytic leukemia cells) and primary monocyte chemotaxis (70 and 50 %, respectively). BNP did not interfere with MCP1 receptor expression or with calcium. BNP inhibited activation of the cytoskeletal protein RhoA in MCP1-stimulated THP1 (70 %). Finally, BNP failed to inhibit MCP1-directed motility of monocytes from patients with hypertension (n = 10) and HF (n = 6) suggesting attenuation of this anti-inflammatory mechanism in chronic heart disease. We provide novel evidence for a direct role of BNP/NPRA in opposing human monocyte migration and support a role for BNP as a cardio-protective hormone up-regulated as part of an adaptive compensatory response to combat excess inflammation.
authors.affiliation: School of Medicine and Medical Science, UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Glezeva
authors.forename: Patrick
authors.initials: P
authors.lastname: Collier
authors.forename: Victor
authors.initials: V
authors.lastname: Voon
authors.forename: Mark
authors.initials: M
authors.lastname: Ledwidge
authors.forename: Kenneth
authors.initials: K
authors.lastname: McDonald
authors.forename: Chris
authors.initials: C
authors.lastname: Watson
authors.forename: John
authors.initials: J
authors.lastname: Baugh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D017461:Receptors, Atrial Natriuretic Factor / Q000819:agonists / Q000378:metabolism; D054390:Receptors, CCR2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2; C058930:brain natriuretic peptide receptor; D020097:Natriuretic Peptide, Brain; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein; D017461:Receptors, Atrial Natriuretic Factor; D002118:Calcium