L-selectin mechanochemistry restricts neutrophil priming in vivo

Zhenghui Liu, Tadayuki Yago, Nan Zhang, Sumith R. Panicker, Ying Wang, Longbiao Yao, Padmaja Mehta-D’souza, Lijun Xia, Cheng Zhu and Rodger P. McEver ()
Additional contact information
Zhenghui Liu: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
Tadayuki Yago: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
Nan Zhang: University of Oklahoma Health Sciences Center
Sumith R. Panicker: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
Ying Wang: University of Oklahoma Health Sciences Center
Longbiao Yao: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
Padmaja Mehta-D’souza: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
Lijun Xia: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
Cheng Zhu: Georgia Institute of Technology
Rodger P. McEver: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract Circulating neutrophils must avoid premature activation to prevent tissue injury. The leukocyte adhesion receptor L-selectin forms bonds with P-selectin glycoprotein ligand-1 (PSGL-1) on other leukocytes and with peripheral node addressin (PNAd) on high endothelial venules. Mechanical forces can strengthen (catch) or weaken (slip) bonds between biological molecules. How these mechanochemical processes influence function in vivo is unexplored. Here we show that mice expressing an L-selectin mutant (N138G) have altered catch bonds and prolonged bond lifetimes at low forces. Basal lymphocyte homing and neutrophil recruitment to inflamed sites are normal. However, circulating neutrophils form unstable aggregates and are unexpectedly primed to respond robustly to inflammatory mediators. Priming requires signals transduced through L-selectin N138G after it engages PSGL-1 or PNAd. Priming enhances bacterial clearance but increases inflammatory injury and enlarges venous thrombi. Thus, L-selectin mechanochemistry limits premature activation of neutrophils. Our results highlight the importance of probing how mechanochemistry functions in vivo.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms15196 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15196

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms15196

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().