Effect of alpha-1-proteinase inhibitor on neutrophil chemotaxis.
Factors that modulate neutrophil migration into the lung are poorly understood. However, there is evidence that neutrophil activation by formylmethionylleucylphenylalanine (FMLP) depends upon a surface proteinase with chymotrypsin-like activity. This suggests that chymotrypsin inhibitors such as alpha-1-proteinase inhibitor (alpha 1PI) could modify neutrophil migration in response to FMLP. We have studied neutrophil chemotaxis using the multiple blind well assay system. This article presents evidence that alpha 1PI is an inhibitor of neutrophil migration in response to FMLP. The effect is related to the inhibitory function of the protein. Alpha-1-antichymotrypsin is more potent than alpha 1PI as an inhibitor of this movement, whereas antileukoprotease is less potent. The results suggest that a cell membrane-bound serine proteinase (perhaps cathepsin G) is necessary for the enhancement of cell movement after receptor binding of FMLP. Oxidized alpha 1PI or a 4,000-D peptide cleaved from alpha 1PI by porcine pancreatic elastase or human neutrophil elastase are capable of enhancing cell motility. The results suggest that alpha 1PI may play a role in cell migration into the lung during acute inflammatory process.
Stockley
R A
RA
Lung Immunobiochemical Research Laboratory, General Hospital, Birmingham, United Kingdom.
Shaw
J
J
Afford
S C
SC
Morrison
H M
HM
Burnett
D
D
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D000514:alpha 1-Antichymotrypsin / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000378:metabolism / Q000494:pharmacology*
D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D015842:Serine Proteinase Inhibitors; D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin; D009240:N-Formylmethionine Leucyl-Phenylalanine