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INDUCTION AND REGULATION OF MONOCYTE PROCOAGULANT ACTIVITY

SZABO, GYONGYI; MILLER-GRAZIANO, CAROL L.
Transplantation: August 1990
THE INCIDENCE OF ANTIMONOCYTE ALLOANTIBODIES: PDF Only

Monocyte (MØ) procoagulant activity (PCA) is induced by various stimuli including allogeneic stimulation, immunocomplexes, and bacterial products. Antigen-antibody complex stimulation therefore represents a pathway for MØ PCA induction. Activation of MØ PCA has been demonstrated in immunocomplex disease and could represent a major pathology in transplanted immunocomplex disease patients. Stimulation of monocytes via their FcRI receptor has been demonstrated to induce TNF and PGE2. This report demonstrates that stimulation of the high-density FcRI receptor-bearing (FcRI+) MØ by rosetting with anti-Rh coated erythrocytes also induces significant PCA levels (P<0.001). Muramyl dipeptide (MDP), a Gram-positive bacterial cell wall analogue, further increased PCA levels in the FcRI stimulated MØ subpopulation (P<0.003). Although increased PCA levels were also induced in the FcRI− MØ subpopulation by MDP (P<0.003), the FcRI+ MØ responded with much greater levels of PCA and PGE2 (P<0.001). Greater PCA levels in the FcRI-positive MØ subpopulation may indicate that stimulation of MØ through their FcRI represents a different pathway from allogenic PCA activation, which can be augmented by subsequent bacterial challenge.A novel inhibitory effect of IL-4 on MØ PCA induction is also demonstrated. IL-4 downregulated MØ PCA levels either after isolation stimulation (55±19%), FcRI stimulation (57±12%), or FcRI plus MDP stimulation (60±13%). PCA and PGE2 levels were concomitantly downregulated by IL-4 both in the FcRI-stimulated, FcRI+ and in the MDP-stimulated FcRI− MØ subpopulations. Since indomethacin blocked MDP induced MØ PGE2 production without affecting MØ PCA levels, PGE2 production is not required for FcRI-stimulated PCA induction.

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