Expression profile of cord blood neutrophils and dysregulation of HSPA1A and OLR1 upon challenge by bacterial peptidoglycan. Issue 1 (28th August 2013)

• Record Type: Journal Article
• Authors: Fong, Oi Ning; Chan, Kathy Yuen Yee; Leung, Kam Tong; Lam, Hugh Simon; Cheung, Hon Ming; Leung, Tak Yeung; Li, Karen; Ng, Pak Cheung
• Is Part Of: Journal of leukocyte biology. Volume 95:Issue 1(2014)
• Page Start: 169
• Page End: 178
• Publication Date: 2013-08-28
• Subjects: human neonate -- differential expression profile -- heat shock proteins -- lipopolysaccharide; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.0413219
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Gene expression and network analysis of cord blood neutrophils upon stimulation by peptidoglycan, and induction mechanism of HSPA1A and OLR1 mediated by NFκB signals. ABSTRACT: In newborn infants, the innate cellular system plays a crucial role in the first line of defense against pathogens. Neutrophils are the most abundant leukocytes, and their response to the commonly encountered nosocomial bacterial (Gram positive) infection in newborns remains largely unclear. In this study, a genome-wide expression array analysis was performed on CB neutrophils after challenge by PGN in vitro and compared with neutrophils in CTL cultures without PGN. We investigated responses of neutrophils to PGN and LPS, with respect to cytokine synthesis, chemotaxis, ROS production, cell death, and pathways of HSP response. Our results provide the first comprehensive expressional profile of neonatal neutrophils stimulated by PGN. mRNA levels of 16 up-regulated genes and 6 down-regulated genes were validated by qPCR. Their regulatory networks were identified downstream of TLR-2 and NOD-2, which work in concert toward signals of death, cytoprotection, inflammation, and stress responses. Members of the HSP family were significantly up-regulated in PGN-stimulated neutrophils, compared with those in LPS-stimulated cells. We confirmed protein co-precipitation of HSPA1A and OLR1 in stimulated neutrophils, and their transcription, induced by NF-κB but not by MAPK signals. We found increased CD11b, chemotaxis, TNF-α, and IL-8 in neutrophils stimulated by PGN or LPS. PGN, but not LPS, increased ROS production. We conclude that neonatal neutrophils are capable of vigorous molecular and functional responses to PGN and suggest that HSP plays a critical role in the host defense mechanism, possibly involving proinflammatory OLR1 and CD11b-facilitated chemotaxis.