Evaluation of elastase and alpha 1-proteinase inhibitor-elastase uptake by polymorphonuclear leukocytes and evidence of an elastase-specific receptor.
Neither resting nor stimulated isolated human polymorphonuclear leukocytes did bind or ingest preformed complexes of alpha 1-proteinase inhibitor and unlabeled/125I-labeled human leukocyte elastase. In contrast, granulocytes bound unlabeled/125I-labeled elastase and the extent of binding was reduced in the presence of respiratory burst stimulators, such as 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, E. coli endotoxin, and N-formyl-L-methionyl-L-leucyl-L-phenylalanine. In association/dissociation and competition inhibition experiments it was demonstrated that granulocyte-elastase binding was specific and saturable. From Scatchard and non-linear regression analysis there was evidence of a two-class receptor model with independent binding sites. Calculated by the non-linear regression method assuming a two-class receptor model the characteristics of the high affinity/low capacity binding site were K1 = 216 +/- 129 X 10(6) l X mol-1 (means +/- s; n = 3) and R1 = 1.38 +/- 0.95 nmol X l-1 corresponding to 0.083 X 10(6) receptors per cell, whereas the low affinity/high capacity binding site had the characteristics K2 = 0.50 +/- 0.09 X 10(6) l X mol-1 and R2 = 237 +/- 103 nmol X l-1 corresponding to 14.3 +/- 6.2 X 10(6) receptors per cell.
D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism*; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D008954:Models, Biological; D009391:Nephelometry and Turbidimetry; D009504:Neutrophils / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D015054:Zymosan / Q000032:analysis; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D007457:Iodine Radioisotopes; D000515:alpha 1-Antitrypsin; D015054:Zymosan; D010196:Pancreatic Elastase