894 Immune Complex - Induced Monocyte Procoagulant Response

The coagulation pathways not only serve hemostatic functions but also appear to be important participants in inflammatory responses, including certain immunologically induced tissue lesions. Local deposition of fibrin is characteristically an early and active process in the immunologic lesions of experimental allergic encephalomyelitis (1, 2), acute proliferative glomerulonephritis (3), delayed cutaneous hypersensitivity (4, 5), and the rheumatoid synovium (6). As one possible mechanism for this phenomenon, it has been observed that human lymphoid cells respond in vitro to diverse immunologic stimuli by generation of cellular procoagulant activity (PCA), 1 an effector limb culminating in the generation of fibrin. Whereas C5a (7), lectins (8), bacterial lipopolysaccharide (LPS) (9), and allogeneic cells (10) have all been described to induce a procoagulant response in vitro, only more recently has it been suggested that immune complexes also possess this potential (8, 11). Rothberger et al. (1 1) observed a small but significant PCA response of human peripheral blood mononuclear cells to aggregated IgG or soluble immune complexes in antigen excess. Prydz et al. (8) have suggested that immune complexes may directly stimulate the monocyte to produce PCA. Studies of LPS-induced PCA have provided evidence that the human monocyte is the source of PCA (12, 13). It has also been established that in murine splenic cells stimulated by LPS, the macrophage contains the PCA product (14). In addition, lymphocyte collaboration was strictly required for the induction of splenic macrophage PCA. We have recently suggested in a preliminary report (15) that PCA generated by human peripheral blood mononuclear cells (PBM) can be localized to the monocyte and requires lymphocyte collaboration. Edwards and Rickles (12) have presented evidence for a lymphokine-mediated mechanism in generating a PCA response to LPS and lectin, and have suggested that the lymphocyte may play a facilitating but not a requisite role. In contrast, Prydz et al. (13) suggest that human monocytes are autonomous in the procoagulant response to various stimuli. In the present study, we investigate the cellular pathways by which soluble immune