1152 Monocyte Procoagulant Activity by Murine Hepatitis

Macrophages play a central role in the pathogenesis of many chronic inflammatory lesions (1). By virtue of their functions, strategic location, and wide tissue distribution, these cells can determine susceptibility and resistance to infection. It appears that macrophages can delay and prevent the spread of infection to susceptible cells. However, where infectious agents with cytopathic properties can replicate freely within macrophages, widespread destruction of tissues may follow. Furthermore, infected circulating macrophages can disseminate infection by migration through the vascular compartment, with distribution of an infectious agent to susceptible organs. Inf lammatory lesions may also result from a series of events starting with the direct interaction of infectious agents with the macrophage. This results in the production of monokines, which stimulate T cells to release lymphokines, which stimulate the macrophage bearing the infectious agent, e.g., listeria monocytogenes (2, 3). Macrophages, in addition to their phagocyte functions, can secrete substantial quantities of hydrolytic enzymes as well as other biologically active products in response to inflammatory stimuli. Such products may contribute to the pathogenetic process (4). A second host defense system that may be activated in response to infection is the coagulation system. The consumption of proteins of the coagulation pathways coupled with the local or disseminated intravascular formation or deposition of fibrin is of diagnostic significance in a number of lesions, including acute proliferative glomerulonephritis (5), Henoch-Schonlein purpura (6), hyperacute renal allograft rejection (7), acute tubular necrosis (8), lupus erythematosus (9), and the Shwartzmann reaction (10). The perivascular deposition of fibrin is one of the earliest features of experimental allergic encephalomyelitis (11). Activation of the coagulation system is frequently associated with active rheumatoid arthritis and other connective tissue diseases (12). Cells of the lymphoreticular system possess low basal procoagulant activity of a poorly defined character; however, significant procoagulant activity (PCA) 1 can be * Publication 2476 from the Immunology Department. Supported by grant CA-28166 from the National Cancer Institute, grant NS 15211 from the National Institutes of Health, and a grant from the National Multiple Sclerosis Society. :~ Recipient of a Medical Research Council of Canada schlolarship. Present address is Department of Medicine, University of Toronto, Toronto, Canada. § Recipient of National Institutes of Health Teacher Investigator award NS 0048. l Abbreviations used in this paper: DMEM, Dulbecco's modified Eagle's medium; FCS, fetal calf serum; LDs0, lethal dose 50%; LPS, lipopolysaccharide; MHV-3, murine hepatitis virus type 3; MOI, multiplicity of infection; PBM, peripheral blood mononuclear cells; PCA, procoagulant activity; PFU, plaque-forming units.