Abstract
The relationship between receptor-ligand interaction in human neutrophils and initiation of enhanced Ca permeability ("45Ca uptake") has been correlated with cell function. Different ligands varied in their efficacy in provoking 45Ca permeability changes: chemotactic peptide f-Met-Leu-Phe greater than concanavalin A greater than immune complexes greater than phorbol myristate acetate. Mixtures of stimuli at optimal concentrations elicited no summation of responses, indicating that interaction of f-Met-Leu-Phe, concanavalin A, and phorbol myristate acetate with their respective "receptors" regulates a common site of 45Ca uptake. The onset of Ca uptake was an early event, preceding onset of aggregation, O-2 generation, and degranulation. Enhanced 45Ca permeability during neutrophil activation is dependent on mobilization of intracellular Ca, since 8-(N,N-diethylamino)-octyl:3,4,5-trimethoxybenzoate hydrochloride was a potent inhibitor of the Ca permeability response. In contrast, calmodulin antagonists did not inhibit Ca permeability changes; the requirement for calmodulin in the physiological responses of aggregation, O-2 generation, and degranulation must therefore be subsequent to activation of the "Ca translocator." We propose a role for a "Ca-translocating mechanism" as an amplifying factor in neutrophil activation.
Highlights
The relationshipbetweenreceptor-ligandinterac- have stressed changes in calcium permeability activated by tion in human neutrophils and initiation of enhanced chemotactic peptides such as f-Met-Leu-Phe [13, 14]
Calmodulin antagonists did not cation mechanisms associated with that particular receptor inhibit Ca permeability changes; the requirement for or if the different receptors interact with a commonCa calmodulin in the physiological responses of aggrega- translocation site [15]
We propose a rolefor a “Ca-translocating mechanism”other physiological responses and aretherefore appropriately as an amplifying factor in neutrophil activation. placed in the activation sequence to act as an amplifying mechanism
Summary
Tion, 0; generation, and degranulation must In this study, we show that a variety of stimuli provoke be subsequent to activation of the “Ca translocator.” rapid changes in Ca permeability which precede the onset of. We propose a rolefor a “Ca-translocating mechanism”other physiological responses and aretherefore appropriately as an amplifying factor in neutrophil activation. Interaction of appropriate stimuli with a common Ca translocating site Activation of their specific receptors initiates the activation of responses this Ca translocating site appears to be dependent on changes such as superoxide anion (0;g)eneration, degranulation (l), in intracellular Ca, but is not calmodulin-dependent. The neutrophil is an interesting cell in which to study the role of changes in Ca permeability following ligand-receptor interaction, because several different ligand-receptor systems.
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