EOSINOPHIL GRANULE PROTEINS INHIBIT SUBSTANCE-P-INDUCED HISTAMINE-RELEASE FROM HUMAN SKIN MAST-CELLS

[摘要] We have investigated the activity of the four principal cationic proteins of the eosinophil granules, major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin, and eosinophil cationic protein on histamine release from human skin mast cells. These four cationic proteins, over the concentration range of to to 200 mu g/ml, did not induce significant histamine release, nor did they prime anti-IgE-induced histamine release from human skin mast cells significantly. However; a brief incubation (15 minutes) of two of the four principal eosinophil granule proteins, MBP and EPO, at concentrations of 50 to 200 mu g/ml, caused a significant concentration-related inhibition of histamine release induced by 30 mu mol/L substance P. The concentrations producing 50% inhibition for MBP and EPO on substance P-induced histamine release were 30 mu g/ml and 100 mu g/ml, respectively. This inhibitory effect appears to be a direct effect of these proteins on skin mast cells because purified (78% to 85%) skin mast cells displayed a similar response to MBP and EPO (n = 4). Also when skin mast cells were incubated with 100 mu g/ml MBP and EPO for is minutes and washed twice before activation by substance P, the inhibitory effect was not altered. These two proteins also inhibited histamine release induced by 10 mu g/ml compound 48/80. These results suggest that MBP and EPO affect the same binding site(s) on skin mast cells as those of substance P.

[发布日期] 1994-05-01

[关键词] EOSINOPHIL GRANULE PROTEINS;MAJOR BASIC PROTEIN (MBP);EOSINOPHIL PEROXIDASE (EPO);EOSINOPHIL-DERIVED NEUROTOXIN (EDN);EOSINOPHIL CATIONIC PROTEIN (ECP);HUMAN SKIN MAST CELLS;SUBSTANCE P;HISTAMINE RELEASE