AJP - Lung Cellular and Molecular Physiology, Vol 267, Issue 1 71-L78, Copyright © 1994 by American Physiological Society
Alteration of cellular cytosolic calcium and chemotactic peptide binding by an inhibitor of neutrophil function
J. A. Cooper Jr, T. A. Bridges, J. I. Kennedy Jr and R. Culbreth
Pulmonary Division, Birmingham Department of Veterans Affairs Medical Center 35233.
The lung is frequently exposed to particulate material that can potentially
stimulate release of factors that attract polymorphonuclear neutrophils
(PMN). However, few PMN are noted in the airways of normal subjects,
suggesting there is some mechanism to dampen influx of these cells. We have
isolated from bronchial lavage a peptide that inhibits PMN chemotaxis to
formyl-methionyl-leucyl-phenylalanine (FMLP). In the present study we
examined effects of this molecule on 1) chemotaxis to other agonists, 2)
FMLP-stimulated PMN superoxide production, 3) PMN calcium fluxes, and 4)
binding of FMLP. Our results show that purified inhibitor attenuates PMN
chemotaxis to C5a and leukotriene B4. This molecule also inhibits PMN
superoxide release in response to FMLP. Exposure to this inhibitor causes
an abrupt rise in cytosolic calcium concentration due to a pertussis
toxin-sensitive shift of intracellular calcium and attenuates subsequent
influx of extracellular calcium in response to FMLP. Binding studies
demonstrate the inhibitor induces increased FMLP binding at 37 degrees C
but has no effects at 4 degrees C. Inhibition of chemotaxis and increased
FMLP binding mediated by this molecule are attenuated by buffering PMN
calcium transients. These studies suggest an inhibitor of neutrophil
function present in the bronchial environment alters PMN through effects on
calcium homeostasis.
