CD11b/CD18 integrin and a beta-glucan receptor act in concert to induce the synthesis of platelet-activating factor by monocytes.
We determined the mechanism by which opsonized zymosan particles, which are derived from yeast and composed of carbohydrate polymers, stimulate platelet-activating factor (PAF) synthesis by monocytes. A role for CD11b/CD18 was demonstrated because antibodies to this integrin decreased PAF synthesis, zymosan bearing only a ligand for CD11b/CD18 (iC3b) induced the synthesis of PAF, and monocytes that did not express CD11b/CD18 produced much less PAF than control monocytes. Ligation of CD11b/CD18 was not sufficient for PAF synthesis suggesting that an additional receptor was involved. Monocytes are known to bind beta-glucan which is a major component of zymosan. Opsonized beta-glucan particles stimulated the synthesis of PAF, and a soluble form of beta-glucan partially inhibited PAF synthesis in response to opsonized zymosan. Two lines of evidence suggested that the beta-glucan receptor mediating this response was distinct from CD11b/CD18. First, CD11b/CD18-deficient monocytes produced PAF when stimulated by zymosan opsonized with isolated C3b, a molecule that binds to complement receptor type 1 (CD35). Second, inducing contact of monocytes with zymosan by centrifugation resulted in PAF synthesis that was not inhibited by antibodies to CD11b/CD18. The combination of soluble beta-glucan and antibodies to CD11b/CD18 completely blocked PAF synthesis in response to opsonized zymosan. Together, these results demonstrate that induction of maximal PAF synthesis by serum-opsonized zymosan requires the concerted interactions of monocyte receptors for iC3b and beta-glucan. Additionally, they suggest that CD11b/CD18 facilitates binding of the particle and that a beta-glucan receptor transduces the activation signal.
Elstad
M R
MR
Department of Medicine, Veterans Affairs Medical Center, Salt Lake City, UT.
Parker
C J
CJ
Cowley
F S
FS
Wilcox
L A
LA
McIntyre
T M
TM
Prescott
S M
SM
Zimmerman
G A
GA
D015703:Antigens, CD / Q000502:physiology*; D018821:CD18 Antigens; D006801:Humans; D066298:In Vitro Techniques; D016177:Macrophage-1 Antigen / Q000502:physiology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009895:Opsonin Proteins / Q000502:physiology; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D011971:Receptors, Immunologic / Q000502:physiology*; D015054:Zymosan / Q000276:immunology
D015703:Antigens, CD; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D010972:Platelet Activating Factor; D011971:Receptors, Immunologic; C045268:beta-glucan receptor; D015054:Zymosan