Human neutrophils contain and bind high molecular weight kininogen.
Because plasma kallikrein activates human neutrophils, and in plasma prekallikrein (PK) circulates complexed with high molecular weight kininogen (HMWK), we determined whether HMWK could mediate kallikrein's association with neutrophils. HMWK antigen (237 +/- 61 ng HMWK/10(8) neutrophils) was present in lysates of washed human neutrophils. Little if any plasma HMWK was tightly bound and nonexchangeable with the neutrophil surface. Human neutrophils were found to possess surface membrane-binding sites for HMWK but no internalization was detected at 37 degrees C. 125I-HMWK binding to neutrophils was dependent upon Zn2+. Binding of 125I-HMWK to neutrophils was specific and 90% reversible. 125I-HMWK binding to neutrophils was saturable with an apparent Kd of 9-18 nM and 40,000-70,000 sites per cell. Upon binding to neutrophils, 125I-HMWK was proteolyzed by human neutrophil elastase (HNE) into lower relative molecular mass derivatives. Furthermore, HMWK found in neutrophils also served as a cofactor for HNE secretion because neutrophils deficient in HMWK have reduced HNE secretion when stimulated in plasma deficient in HMWK or with purified kallikrein. These studies indicate that human neutrophils contain a binding site for HMWK that could serve to localize plasma or neutrophil HMWK on their surface to possibly serve as a receptor for kallikrein and to participate in HNE secretion by this enzyme.
Gustafson
E J
EJ
Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Schmaier
A H
AH
Wachtfogel
Y T
YT
Kaufman
N
N
Kucich
U
U
Colman
R W
RW
D000941:Antigens / Q000032:analysis; D002413:Cations, Divalent; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007610:Kallikreins / Q000097:blood; D007704:Kininogens / Q000276:immunology / Q000378:metabolism*; D019272:Leukocyte Elastase; D008970:Molecular Weight; D009504:Neutrophils / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism
D000941:Antigens; D002413:Cations, Divalent; D007704:Kininogens; D007610:Kallikreins; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase