Comparison of cytosolic calcium shifts, superoxide generation, and lactoferrin secretion in the neutrophils of atopics and nonatopics.
We previously found that platelet-activating factor (PAF) stimulated greater lactoferrin secretion by neutrophils of atopics than nonatopics. To help understand underlying mechanisms, we compared agonist-stimulated lactoferrin secretion with another response, superoxide generation, to determine whether there is a global alteration in the reactivity of atopic neutrophils to these stimuli. We also determined Ca2+ mobilization in such neutrophils because such mobilization is a signaling pathway for both superoxide generation and granule content exocytosis. Although PAF again stimulated greater lactoferrin secretion in atopic than in nonatopic neutrophils, the peak superoxide secretion and cytosolic Ca2+ mobilization were not significantly different in atopics and nonatopics. Leukotriene B4-induced superoxide secretion and cytosolic Ca2+ shifts were also similar in atopics and nonatopics. These findings suggest that (1) the enhanced PAF-induced lactoferrin secretion in atopic neutrophils is not a reflection of greater PAF binding or broad-based cell hyperreactivity and (2) a selective signaling pathway in atopic neutrophils may be responsible for the enhanced lactoferrin secretion. These findings may be relevant to in vivo events because we have found increased PAF and lactoferrin release in skin chambers overlying immunoglobulin E-mediated human skin reactions.
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6057.
B
B
Zweiman
C
C
von Allmen
A
A
Moskovitz
P
P
Atkins
M
M
Taylor
H
H
Korchak
D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood*; D007781:Lactoferrin / Q000097:blood*; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D013481:Superoxides / Q000097:blood*
D010972:Platelet Activating Factor; D013481:Superoxides; D007781:Lactoferrin; D002118:Calcium