Thrombin generates monocyte chemotactic activity from complement factor H.
We have recently found that the complement factor H (H) was the precursor of the major macrophage chemotactic factor in the delayed-type hypersensitivity (DTH) reaction site in the skin and was converted to the factor by an unidentified trypsin-like protease in plasma. Thrombin and plasmin are also present in the site, and we, therefore, examined the possibility that these proteases converted H to be monocyte chemotactic. Intact H caused no monocyte migration, although it was able to do so after incubation with thrombin, but not with plasmin. The activity was chemotactic rather than chemokinetic and was absorbed by an anti-H IgG-conjugated column. The generation of monocyte chemotactic activity from H was dependent on incubation time with thrombin and also the protease activity of thrombin, and the activity was seen at concentrations of H lower than 10(-8) M. The inhibitory activity of H for C3b-Bb was not affected by incubation with thrombin or plasmin. Incubation of H with thrombin, but not with plasmin, generated a hydrophobic molecule, in a time-dependent manner, which had monocyte chemotactic activity. These results show that H becomes a monocyte chemotactic factor due to cleavage by thrombin, which converts H to a more hydrophobic molecule and also suggest that thrombin-treated H induces monocyte migration in the DTH reaction site.
Ohtsuka
H
H
Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Japan.
Imamura
T
T
Matsushita
M
M
Tanase
S
S
Okada
H
H
Ogawa
M
M
Kambara
T
T
D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003179:Complement C3b / Q000276:immunology; D017242:Complement Factor H / Q000276:immunology*; D005341:Fibrinolysin / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D013917:Thrombin / Q000276:immunology*
C493495:CFH protein, human; D007074:Immunoglobulin G; D003179:Complement C3b; D017242:Complement Factor H; D013917:Thrombin; D005341:Fibrinolysin