Extensive hydrolysis of N-formyl-L-methionyl-L-leucyl-L-[3H] phenylalanine by human polymorphonuclear leukocytes. A potential mechanism for modulation of the chemoattractant signal.

Journal Article (Journal Article)

Chemoattractant receptors on human polymorphonuclear leukocytes (PMNs) stimulate a series of important biological responses. In an attempt to better understand the mechanism of stimulus response coupling of chemoattractant receptors, the kinetics of N-formyl-L-methionyl-L-leucyl-L-[3H]phenylalanine (fMet-Leu-[3H]Phe) binding to PMNs was evaluated. Unexpectedly, extensive degradation of the ligand was found to occur rapidly at 37 degrees C. Exposure of 10(7) cells/ml to 10 nM fMet-Leu-[3H]Phe led to the specific uptake of approximately 1% of the ligand within 10 min, while approximately 50% of the extracellular chemoattractant was hydrolyzed to free amino acids. Under the same conditions, isolated plasma membranes equivalent to 2.5 X 10(7) PMNs/ml bound specifically approximately 1% of the ligand and degraded about one-half of it primarily to Leu-[3H]Phe. The fMet-Leu-[3H]Phe hydrolysis commenced with no apparent latency, yet disobeyed first order kinetics as a 100-fold excess unlabeled ligand enhanced the initial consumption rate of 10 nM fMet-Leu-[3H]Phe by 500-fold, yielding an enhancement of the relative hydrolysis to approximately 70%. 1-butanol at 0.25%, which accelerates chemotaxis but inhibits superoxide anion and lysosomal enzyme secretion, reduced the hydrolysis to about 15% independent of the fMet-Leu-[3H]Phe specific activity. Lysosomal secretion could not mediate the hydrolysis process, since the supernatants of PMNs exposed either to 10 nM of 1 microM fMet-Leu-Phe reveal no degradation capacity toward fMet-Leu-[3H]Phe. These data indicate that the hydrolysis of the chemoattractant occurs at the cell surface and is dependent on the plasma membrane physical state. This phenomenon may well modulate the chemotactic signal due to its ability to profoundly alter the level of the chemoattractant proximate to the cell surface.

Full Text

Duke Authors

Cited Authors

  • Yuli, I; Snyderman, R

Published Date

  • April 15, 1986

Published In

Volume / Issue

  • 261 / 11

Start / End Page

  • 4902 - 4908

PubMed ID

  • 3957916

International Standard Serial Number (ISSN)

  • 0021-9258


  • eng

Conference Location

  • United States