Adherence of human monocytes to haemodialysis membranes: LFA 1 (CD11a/CD18) CR1 (CD35) and CR3 (CD11b/CD18) triggering promotes the biosynthesis of platelet-activating factor and adherence.
BACKGROUND
Platelet-activating factor is a mediator of inflammation involved in the blood-membrane interaction. We report that selective stimulation of complement receptors (CR1 and CR3) triggers PAF synthesis and monocyte adherence to complement-activating membranes.


METHODS
The synthesis of PAF was studied after stimulation of normal human adherent monocytes with F(ab)2 and Fab fragments of monoclonal antibodies specific to CR1 and CR3. CD11a, CD11b, CD18, and CD35 was studied by flow cytometry on neutrophils and monocytes. The molecular species of PAF from stimulated monocytes were identified by reverse-phase high-performance liquid chromatography coupled with mass spectrometry.


RESULTS
Anti-CR1 and anti-CR3 monoclonal antibodies induced a dose-dependent C-16 but not C-18 PAF production. The latter occurred also with monovalent Fab fragments of both anti-CR1 and anti-CR3 monoclonal antibodies, that were not internalized as seen by immunofluorescence. Adherence of monocytes to Cuprophan membranes was markedly higher (P < 0.01) in membranes pretreated with fresh than with heat-inactivated normal plasma. However, the high adherence to fresh plasma-treated membranes was completely abrogated by coincubating the cells with Web 2170, a specific PAF receptor antagonist. This was not due to downregulation of adhesion molecules expression on leukocytes.


CONCLUSIONS
These studies implicate a crucial role of PAF in blood interaction with haemodialysis membranes that fix complement activated products.
Tetta
C
C
Clinical and Laboratory Research Department, Bellco S.p.A., Mirandola, Modena.
Tropea
F
F
Camussi
G
G
Neri
R
R
Wratten
M L
ML
Sereni
L
L
Silvestro
L
L
Franceschi
C
C
Haeffner-Cavaillon
N
N
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology* / Q000502:physiology*; D002478:Cells, Cultured; D002482:Cellulose / Q000009:adverse effects / Q000031:analogs & derivatives; D003167:Complement Activation; D006801:Humans; D066298:In Vitro Techniques; D007688:Kidneys, Artificial / Q000009:adverse effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008567:Membranes, Artificial; D009000:Monocytes / Q000276:immunology* / Q000502:physiology*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D017463:Receptors, Complement 3b / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D008567:Membranes, Artificial; D010972:Platelet Activating Factor; D017463:Receptors, Complement 3b; D002482:Cellulose; C009865:cuprammonium cellulose