Azotemia, TNFα, and LPS prime the human neutrophil oxidative burst by distinct mechanisms

Kenneth R. Mcleish, Jon B. Klein, Eleanor D. Lederer, Kimberly Z. Head, Richard A. Ward

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The oxidative burst of neutrophils from azotemic patients (AzoPMNs) is primed for an enhanced response compared to neutrophils from normal subjects (NorPMNs). The mechanism for this priming is unknown, although TNFα does not further prime AzoPMNs. The present study examines the hypothesis that azotemia and TNFα prime neutrophils by the same mechanism. Formyl peptide receptor expression and degranulation were not primed in AzoPMNs, but were primed by both LPS and TNFα. LPS was also able to prime the AzoPMN oxidative burst. Guanine nucleotide exchange by multiple guanine nucleotide binding proteins, including heterotrimeric G-proteins and low molecular weight GTP-binding proteins (LMWGs), was increased in AzoPMNs, as demonstrated by GTPγS binding and azidoanilide GTP photoaffinity labeling. The plasma membrane density of G-protein α(i2), α(i3), and α(s) subunits and the density in the cytosol of the LMWG, Rac2, did not differ between AzoPMNs and NorPMNs. However, the LMWG, Rap1A, was present in significantly greater amounts on plasma membranes from AzoPMNs. FMet-Leu-Phe-stimulated phospholipase D activity, but not basal activity, was significantly greater in AzoPMNs. Finally, incubation of NorPMNs in plasma from azotemic patients resulted in a significant increase in basal GTPγS binding. These results demonstrate that priming of AzoPMNs is restricted to oxidative burst activity and that it occurs by a mechanism distinct from that utilized by TNFα and LPS. While the exact mechanism remains unknown, it appears to involve a plasma factor and changes in LMWG expression or activity.

Original languageEnglish (US)
Pages (from-to)407-416
Number of pages10
JournalKidney international
Volume50
Issue number2
DOIs
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Azotemia, TNFα, and LPS prime the human neutrophil oxidative burst by distinct mechanisms'. Together they form a unique fingerprint.

Cite this