The complement factor properdin induces formation of platelet-leukocyte aggregates via leukocyte activation.
Both the complement system and platelet-leukocyte aggregates are involved in chronic and acute stages of atherosclerosis. Properdin, a positive regulator of the complement system, is secreted by leukocytes and endothelial cells. In the present study, the role of properdin in the formation of platelet-leukocyte aggregates was investigated. Incubation of human whole blood with properdin (25-200 microg/ml) resulted in a dose-dependent formation of platelet-leukocyte aggregates, with an increase of up to 2.2-fold compared to controls (p < 0.05), as analysed by flow cytometry. In addition, properdin significantly amplified ADP-induced aggregation of platelets with leukocytes by 53% (p < 0.05), while it had no effect on ADP-induced aggregation of platelets alone. Consistent with these results, properdin did not activate platelets as shown by the expression of activated GPIIb/IIIa (PAC-1 epitope) and P-selectin (CD62P) on the platelet surface. However, properdin significantly induced expression of CD11b (MAC-1) on leukocytes by 12-fold (p < 0.05) as a measure of leukocyte activation. In conclusion, the complement system component properdin induces the formation of platelet-leukocyte aggregates via leukocyte activation. The data establish a link between the complement system and platelet-leukocyte aggregates with potential significance in atherosclerotic vascular disease.
Ruef
Johannes
J
Red Cross Hospital Cardiology Center, Frankfurt, Germany.
Kuehnl
Peter
P
Meinertz
Thomas
T
Merten
Michael
M
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D050197:Atherosclerosis / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D039481:CD11b Antigen / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D003170:Complement Pathway, Alternative; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D019007:P-Selectin / Q000096:biosynthesis / Q000235:genetics; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000096:biosynthesis / Q000235:genetics; D011414:Properdin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology
D039481:CD11b Antigen; C509295:ITGAM protein, human; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011414:Properdin; D000244:Adenosine Diphosphate