Regulation of human neutrophil aggregation: comparable latent times,
activator sensitivities, and exponential decay in aggregability for FMLP,
platelet-activating factor, and leukotriene B4
YP Rochon and MM Frojmovic
Department of Physiology, McGill University, Montreal, Quebec, Canada.
We have recently described a flow cytometry technique, whose sensitivity
allows direct measurements of latent times before the onset of aggregation,
and of rates, maximal extents, and reversibility of aggregation (J Leuk
Biol 50:434, 1991). We report here that activators which stimulate
sustained cellular signaling associated with increases in intracellular
calcium (ionomycin) or protein kinase C activation (phorbol myristate
acetate, PMA) cause complete (> or = 98%) and irreversible neutrophil
aggregation, with latent times for the onset of aggregation inversely
proportional to the activator concentration. In contrast, the
receptor-specific activators leukotriene B4 (LTB4), formyl peptide FMLP,
and platelet-activating factor (PAF) gave only partial and reversible
aggregatory responses, limited by the following similar properties: latent
times of 4.5 seconds +/- 1.5 seconds, independent of activator
concentration; similar concentrations for onset of aggregation
(approximately 1 nmol/L) that increased over a similar broad range of
activator concentration, with one-half maximal rates of aggregation at 10
nmol/L to 30 nmol/L, corresponding to reported dissociation constant
values; comparable limited recruitment and spontaneous reversibility of
aggregation; absence of interactivator synergism; and similar exponential
decays in activated cell stickiness (refractoriness), with t1/2 = 15 to 30
seconds. Variable cross- desensitization was seen between LTB4 and FMLP
depending on donor and activator concentrations. In vivo, these properties
are expected to provide localization of the aggregatory response,
minimizing the otherwise detrimental effects of circulating activated
neutrophils.
Volume 82,
Issue 11,
pp. 3460-3468,
12/01/1993
Copyright © 1993 by The American Society of Hematology
