Inhibition of cell adhesion by high molecular weight kininogen.
An anti-cell adhesion globulin was purified from human plasma by heparin-affinity chromatography. The purified globulin inhibited spreading of osteosarcoma and melanoma cells on vitronectin, and of endothelial cells, platelets, and mononuclear blood cells on vitronectin or fibrinogen. It did not inhibit cell spreading on fibronectin. The protein had the strongest antiadhesive effect when preadsorbed onto the otherwise adhesive surfaces. Amino acid sequence analysis revealed that the globulin is cleaved (kinin-free) high molecular weight kininogen (HKa). Globulin fractions from normal plasma immunodepleted of high molecular weight kininogen (HK) or from an individual deficient of HK lacked adhesive activity. Uncleaved single-chain HK preadsorbed at neutral pH, HKa preadsorbed at pH greater than 8.0, and HKa degraded further to release its histidine-rich domain had little anti-adhesive activity. These results indicate that the cationic histidine-rich domain is critical for anti-adhesive activity and is somehow mobilized upon cleavage. Vitronectin was not displaced from the surface by HKa. Thus, cleavage of HK by kallikrein results in both release of bradykinin, a potent vasoactive and growth-promoting peptide, and formation of a potent anti-adhesive protein.
Departments of Medicine, University of Wisconsin, Madison 53706.
S
S
Asakura
R W
RW
Hurley
K
K
Skorstengaard
I
I
Ohkubo
D F
DF
Mosher
D002413:Cations, Divalent; D002448:Cell Adhesion / Q000187:drug effects*; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007704:Kininogens / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D007705:Kinins; D008970:Molecular Weight; D011498:Protein Precursors / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D019096:Vitronectin; D014841:von Willebrand Factor / Q000378:metabolism
D002413:Cations, Divalent; D005353:Fibronectins; D006023:Glycoproteins; D007704:Kininogens; D007705:Kinins; D011498:Protein Precursors; D019096:Vitronectin; C046022:prekininogens; D014841:von Willebrand Factor; D005340:Fibrinogen