Accession Number:

ADA413640

Title:

Surfactant Releases Internal Calcium Stores in Neutrophils by G Protein-Mediated Pathway

Descriptive Note:

Corporate Author:

AIR FORCE INST OF TECH WRIGHT-PATTERSONAFB OH

Report Date:

2002-10-07

Pagination or Media Count:

35.0

Abstract:

Pulmonary surfactant with surfactant-associated proteins PSSAP decreases pulmonary inflammation by suppression of neutrophil activation. We have observed that PSSAP inserts channels into artificial membranes, depolarizes neutrophils, decreases calcium influx following stimulation, and depresses neutrophil functions in vitro. We hypothesize that PSSAP suppresses neutrophil activation by insertion of cation channels into plasma membrane, depolarization of neutrophils, and 0 protein-dependent release of Oa stores, and that gramicidin - a monovalent, cation channel protein - mimics these effects. Human neutrophils were monitored for Oa1 responses after exposure to gramicidin alone, gramicidin reconstituted with phospholipid PLG, one of two different PSSAP preparations, or a PS-SAP preparation. tOa1 responses were reexamined following preexposure to 0 protein or internal Ca release inhibitors. We observed that 11 PSSAP but not PS-SAP - causes transient increases of neutrophil Oa within seconds of exposure 21 PLG - but not gramicidin alone - closely mimics the effect of PSSAP upon Ca response 3 PSSAP, gramicidin alone and PLG equally depolarizes neutrophils despite differences among neutrophil Oa responses 4 direct inhibition of internal Ca store release or G protein activation suppresses Ca responses to PSSAP and PLO and 5 preexposure to either PSSAP or PLG inhibits Ca influx following tMLP stimulation. We conclude that PSSAP independently depolarizes neutrophils, releases Oa from internal stores by a G protein-mediated pathway, and alters subsequent neutrophil response to physiologic stimulants. The mimicking of these results by PLG supports the hypothesis that PSSAP initiates depolarization via channel insertion into neutrophil plasma membrane.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE