Ammonium decreases human polymorphonuclear leukocyte cytoskeletal actin

B. Brunkhorst, R. Niederman

Research output: Contribution to journalArticlepeer-review

Abstract

Ammonium, a weak base produced as a metabolic by-product of urea metabolism by bacterial pathogens, inhibits a variety of motile polymorphonuclear leukocyte (PMN) functions. It was initially assumed that the mechanism of leukocyte inhibition was due to cytoplasmic alkalinization. However, while it is clear that ammonium can effect cytoplasmic alkalinization, current data indicate that alterations in chemotaxis, degranulation, and receptor recycling occur independently of cytoplasmic alkalinization. Since these are motility-related events, we examined the possibility that alterations in cytoskeletal actin may account for the effects of ammonium on PMN function. The results indicate that ammonium can inhibit degranulation, decrease cytoskeletal actin, and increase actin depolymerization rates. These findings are supported by five lines of evidence. First, formylmethionyl-leucyl-phenylalanine (fMLP)-induced elastase release was inhibited by 85% ± 3% in the presence of ammonium, and ammonium by itself did not stimulate elastase release. Second, ammonium treatment of resting PMNs caused a rapid 38% ± 6% decrease in cytoskeletal actin. Third, ammonium treatment accelerated the fMLP-induced depolymerization phase of the cytoskeletal actin transient by 150% ± 12%. Fourth, in resting PMNs treated with cytochalasin B or D, ammonium induced a 21% ± 4% and a 25% ± 5% decrease in cytoskeletal actin, respectively. Conversely, ammonium did not affect the ability of the cytochalasins to inhibit an fMLP-induced cytoskeletal actin transient. Fifth, pertussis toxin treatment of neutrophils did not affect the ammonium-stimulated decrease in cytoskeletal actin. These results suggest that ammonium can inhibit neutrophil function by altering cytoskeletal actin and therefore provide new information regarding potential pathogenic mechanisms for bacterial pathogens.

Original languageEnglish (US)
Pages (from-to)1378-1386
Number of pages9
JournalInfection and Immunity
Volume59
Issue number4
StatePublished - 1991

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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