Pharmacological control of human basophil histamine release stimulated by eosinophil granule major basic protein.
Eosinophil granule major basic protein (MBP) is a 13,800 MW arginine-rich polypeptide that is unique among basic molecules in its ability to stimulate human basophil histamine release. We examined the Ca2+ requirements and pharmacological regulation of MBP-stimulated histamine release. Minimal MBP-induced histamine release occurred in the absence of extracellular Ca2+, whereas addition of 0.1 mM Ca2+ resulted in 70% of the maximum histamine release response. Maximum histamine release required 0.5 to 1 mM extracellular Ca2+. The MBP-induced histamine release was blocked by a calmodulin antagonist and by theophylline and was partially inhibited by an inhibitor of phospholipase A2. Release was unaffected by inhibition of protein kinase C. Basophil pretreatment with pertussis toxin also resulted in a concentration-dependent inhibition of release, suggesting involvement of a GTP regulatory protein in the activation mechanism. Histamine release stimulated by a 13,900 MW poly-L-arginine exhibited a dissimilar pharmacological profile from that of MBP. These results support the non-cytolytic nature of the MBP activation mechanism and identify pharmacological approaches for control of MBP-induced mediator release.
Thomas
L L
LL
Department of Immunology/Microbiology, Rush Medical College, Chicago, IL 60612.
Zheutlin
L M
LM
Gleich
G J
GJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000098:Acetophenones / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D001798:Blood Proteins; D002118:Calcium / Q000378:metabolism; D047091:Eosinophil Granule Proteins; D004804:Eosinophils; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D037342:Pertussis Toxin; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012260:Ribonucleases; D013449:Sulfonamides / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000098:Acetophenones; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; D010566:Virulence Factors, Bordetella; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013806:Theophylline; D037342:Pertussis Toxin; D011493:Protein Kinase C; D012260:Ribonucleases; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide; D002118:Calcium