Store-operated calcium entry in human neutrophils reflects multiple contributions from independently regulated pathways.
Human polymorphonuclear neutrophil (PMN) responses to G protein-coupled chemoattractants are highly dependent upon store-operated Ca(2+) entry (SOCE). Recent research suggests that SOCE currents can be mediated by a variety of related channel proteins of the transient receptor potential superfamily. SOCE has been regarded as a specific response to depletion of cell calcium stores. We hypothesized that net SOCE might reflect the contributions of more than one calcium entry pathway. SOCE was studied in normal human PMN using Ca(2+) and Sr(2+) ions. We found that PMN SOCE depends on at least two divalent cation influx pathways. One of these was nonspecific and Sr(2+) permeable; the other was Ca(2+) specific. The two pathways show different degrees of dependence on store depletion by thapsigargin and ionomycin, and differential sensitivity to inhibition by 2-aminoethyoxydiphenyl borane and gadolinium. The inflammatory G protein-coupled chemoattractants fMLP, platelet-activating factor, and IL-8 elicit unique patterns of Sr(2+) and Ca(2+) influx channel activation, and SOCE responses to these agonists displayed differing degrees of linkage to prior Ca(2+) store depletion. The mechanisms of PMN SOCE responses to G protein-coupled chemoattractants are physiologically diverse. They appear to reflect Ca(2+) transport through a variety of channels that are independently regulated to varying degrees by store depletion and by G protein-coupled receptor activation.
Itagaki
Kiyoshi
K
Department of Surgery, Division of Trauma, New Jersey Medical School, Newark, NJ 07103, USA.
Kannan
K B
KB
Livingston
David H
DH
Deitch
Edwin A
EA
Fekete
Zoltan
Z
Hauser
Carl J
CJ
D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002413:Cations, Divalent; D002463:Cell Membrane Permeability / Q000502:physiology; D002630:Chemotactic Factors / Q000378:metabolism / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D005682:Gadolinium / Q000502:physiology; D006801:Humans; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D013324:Strontium / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology
D015220:Calcium Channels; D002413:Cations, Divalent; D002630:Chemotactic Factors; D011956:Receptors, Cell Surface; D005682:Gadolinium; D019204:GTP-Binding Proteins; D002118:Calcium; D013324:Strontium