Activation of human eosinophils by platelet-derived growth factor.
Activated eosinophils are believed to be major contributors to the chronic inflammatory sequelae of asthma, but the details of the mechanism of eosinophil activation in vivo are unknown. In our search for physiologically important modes of eosinophil activation, we studied the effects of recombinant human platelet-derived growth factor (PDGF) on human peripheral blood eosinophils. We compared two activation end-points: secretion of granule contents, exemplified by the release of eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), and the generation of active oxygen metabolites (O2- production). PDGFc-sis dose dependently stimulated the secretion of large amounts of EPO and EDN from eosinophils. Higher concentrations of PDGF induced a dose-dependent O2- production, especially if the cells were first primed with low concentrations of phorbol ester. These activities were not seen with the AA homodimer of PDGF, suggesting that the activation was receptor dependent. However, several attempts to directly demonstrate the existence of such receptors were unsuccessful. The magnitude of the secretory response to PDGF, and the realization that eosinophils could be easily exposed to this substance as they travel towards the lung, suggests the possibility that this growth factor may be a physiologically important activator of eosinophils in the pulmonary inflammation which is associated with asthma.
Bach
M K
MK
Hypersensitivity Diseases, Upjohn Company, Kalamazoo, Mich. 49001.
Brashler
J R
JR
Stout
B K
BK
Johnson
H G
HG
Sanders
M E
ME
Lin
A H
AH
Gorman
R R
RR
Bienkowski
M J
MJ
Ishizaka
T
T
D000001:Calcimycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D047209:Eosinophil Peroxidase; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D010978:Platelet Factor 4 / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000032:analysis; D017479:Receptors, Platelet-Derived Growth Factor; D012260:Ribonucleases; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D015054:Zymosan / Q000494:pharmacology
D009498:Neurotoxins; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D013481:Superoxides; D010978:Platelet Factor 4; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D015054:Zymosan; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D017479:Receptors, Platelet-Derived Growth Factor; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases