Jad. Cooper et al., ALTERATION OF CELLULAR CYTOSOLIC CALCIUM AND CHEMOTACTIC PEPTIDE BINDING BY AN INHIBITOR OF NEUTROPHIL FUNCTION, The American journal of physiology, 267(1), 1994, pp. 120000071-120000078
The lung is frequently exposed to particulate material that can potent
ially stimulate release of factors that attract polymorphonuclear neut
rophils (PMN). However, few PMN are noted in the airways of normal sub
jects, suggesting there is some mechanism to dampen influx of these ce
lls. We have isolated from bronchial lavage a peptide that inhibits PM
N chemotaxis to formyl-methionyl-leucyl-phenylalanine (FMLP). In the p
resent study we examined effects of this molecule on 1) chemotaxis to
other agonists, 2) FMLP-stimulated PMN superoxide production, 3) PMN c
alcium fluxes, and 4) binding of FMLP. Our results show that purified
inhibitor attenuates PMN chemotaxis to C5a and leukotriene B-4 This mo
lecule also inhibits PMN superoxide release in response to FMLP. Expos
ure to this inhibitor causes an abrupt rise in cytosolic calcium conce
ntration due to a pertussis toxin-sensitive shift of intracellular cal
cium and attenuates subsequent influx of extracellular calcium in resp
onse to FMLP. Binding studies demonstrate the inhibitor induces increa
sed FMLP binding at 37 degrees C but has no effects at 4 degrees C. In
hibition of chemotaxis and increased FMLP binding mediated by this mol
ecule are attenuated by buffering PMN calcium transients. These studie
s suggest an inhibitor of neutrophil function present in the bronchial
environment alters PMN through effects on calcium homeostasis.