Complement is a highly regulated and intricate proinflammatory system that has been shown to be activated in situations of injury, sepsis, and multiple organ failure. Although these observations have long suggested a role for complement in the response to injury, it is the recent advent of the specific complement inhibitor, sCR1, that has begun to reveal the degree to which complement is involved. Furthermore, as one of the earliest inflammatory systems to respond, complement activation inevitably leads to cellular activation with elaboration of cytokines and oxidants, with worsening of injury and further complement activation.


Alper, C. A., Abramson, N., Johnston, R. B., Jr., Jandl, J. H., and Rosen, F. S. (1970). Increased susceptibility to infection associated with abnormalities of complement-mediated functions and of the third component of complement (C3). N. Engl. J. Med. 282, 349-354. This is the initial report linking complement activation to the defense against microbial invasion. Craddock, P. R., Fehr, J., Brigham, K. L., Kronenberg, R. S., and Jacob, H. S. (1977). Complement and leukocyte-mediated pulmonary dysfunction in hemodialysis. N. Engl. J. Med. 296, 769-774. In this paper, the first link between systemic complement activation and secondary lung injury is made. Ellison, R. T., Kohler, P. F., Curd, J. G., Judson, F. N., and Reller, L. B. (1983). Prevalence of congenital or acquired complement deficiency in patients with sporadic meningococcal disease. N. Engl. J. Med. 308, 913-916. This reports a high incidence of terminal complement pathway proteins as the basis for a common devastating infection. Fearon, D. T. (1978). Regulation by membrane sialic acid of |3-1h-dependent decay-dissociation of amplification C3 convertase of the alternative complement pathway. Proc. Natl. Acad. Sci. USA 75, 1971-1975. This work forms the basis of understanding alternative pathway activation. Fearon, D. T. (1980). Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte. J. Exp. Med. 152, 20-30. This is the initial work describing Complement Receptor Type 1, CR1. Gerard, N. P., and Gerard, C. (1991). The chemotactic receptor for human C5a anaphylatoxin. Nature 349, 614-617. This is the initial description of C5aR.

Hill, J., Lindsay, T. F., Ortiz, F., Yeh, C. G., Hechtman, H. B., and Moore, F. D., Jr. (1992). Soluble complement receptor type 1 ameliorates the local and remote organ injury after intestinal ischemia-reperfusion in the rat. J. Immunol. 149, 1723-1728. This report extends the sCRI findings to include prevention of secondary lung injury Moore, F. D., Jr., Davis, C., Rodrick, M., Mannick, J. A., and Fearon, D. T. (1986). Neutrophil activation in thermal injury as assessed by increased expression of complement receptors. N. Engl. J. Med. 314, 948-953. This report links neutrophil activation to complement activation in this important injury type. Stevens, J. H., O'Hanley, P., Shapiro, J. M., Mihm, F. G., Satoh, P. S., Collins, J. A., and Raffin, T. A. (1986). Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. J. Clin. Invest. 77, 1812-1816. This a report of the first experimental attempts to interfere with complement-activation induced pulmonary injury.

Till, G. O., Johnson, K. J., Kunkel, R. G., and Ward, P. A. (1982). Intravascular activation of complement and acute lung injury. Dependency on neutrophils and toxic oxygen metabolites. J. Clin. Invest. 69, 1126— 1135. This work further develops the relationship between systemic complement activation and secondary lung injury.

Weisman, H. F., Bartow, T., Leppo, M. K., Marsh, H. C., Jr., Carson, G. R., Concino, M. F., Boyle, M. P., Roux, K. H., Weisfeldt, M. L., and Fearon, D. T. (1990). Soluble human complement receptor type 1: In vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis. Science 249, 146-151. This is the first report of the salutary effects of a sCR1 complement inhibitor

Capsule Biography

Dr. Moore trained with Drs. D. T. Fearon and K. F. Austen at the time of the discovery of the mechanism of alternative pathway activation and, subsequently, CR1 and sCR1. His personal work has primarily focused on the detailed mechanisms of complement activation by injured tissue. His current clinical responsibility is as Chief of General and Gastrointestinal Surgery at Brigham and Women's Hospital.

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