MICHAEL J. PABST
PROFESSOR

EDUCATION:
B.S. 1967, Boston College, Chestnut Hill, Massachusetts
Ph.D. 1972, Purdue University, West Lafayette, Indiana
Staff Fellow 1972-1974, National Institutes of Health, Bethesda, Maryland

RESEARCH INTERESTS: We investigate the role of macrophages and neutrophils in resistance to infection. Ordinarily, these cells are in the "resident" state, and have only weak ability to kill pathogens or to cause tissue damage. But when these cells are exposed to bacterial products like lipopolysaccharide or muramyl dipeptide, or to lymphokines like interferon gamma, they become "activated." Activated cells release more toxic oxygen radicals, more hydrolases, and more inflammatory mediators like interleukin-1 and tumor necrosis factor. Thus activated cells kill pathogens better, and also enhance the activity of other cells of the immune system. However, activation also increases the likelihood of damage to host tissue. Therefore, activation is tightly regulated. We are studying biochemical parameters of activation, including protein phosphorylation, membrane depolarization, and Ca2+ movements. We study mechanisms by which successful pathogens prevent activation. We are also studying the inactivation of lipopolysaccharide by neutrophils, which could be a key factor in prevention of shock.

CURRENT RESEARCH SUPPORT:
R01 DE 11125 on "Inactivation of Lipopolysaccharide by Neutrophils" September 1, 1994 - August 31, 1998; $446,767 TDC.

GRADUATE STUDENTS:
University of Colorado, Denver: Carl K. Edwards, III, M.A., 1984
University of Tennessee, Memphis: Demin Wang, Ph.D., 1995

PUBLICATIONS: (only selected publications are listed)
15. Pabst, M.J. and Johnston, R.B., Jr. (1980) Increased production of superoxide anion by macro-phages exposed in vitro to muramyl dipeptide or lipopolysaccharide. J. Exp. Med., 151, 101-104.
17. Pabst, M.J., Cummings, N.P., Shiba, T., Kusumoto, S., and Kotani, S. (1980) Lipophilic derivative of muramyl dipeptide is more active than muramyl dipeptide in priming macrophages to release superoxide anion. Infect. Immun., 29, 617-622.
18. Cummings, N.P., Pabst, M.J., and Johnston, R.B., Jr. (1980) Activation of macrophages for enhanced release of superoxide anion and greater killing of Candida albicans by injection of muramyl dipeptide. J. Exp. Med., 152, 1659-1669.
23. Pabst, M.J., Hedegaard, H.B., and Johnston, R.B., Jr. (1982) Cultured human monocytes require exposure to bacterial products to maintain an optimal oxygen radical response. J. Immunol., 128, 123-128.
26. Sasada, M., Pabst, M.J., and Johnston, R.B., Jr. (1983) Activation of mouse peritoneal macro-phages by lipopolysaccharide alters the kinetic parameters of the superoxide-producing NADPH oxidase. J. Biol. Chem., 258, 9631-9635.
27. Speer, C.P., Pabst, M.J., Hedegaard, H.B., Rest, R.F., and Johnston, R.B., Jr. (1984) Enhanced release of oxygen metabolites by monocyte-derived macrophages exposed to proteolytic enzymes: Activity of neutrophil elastase and cathepsin G. J. Immunol., 133, 2151-2156.
28. Harris, L.K., Pabst, M.J., and Johnston, R.B., Jr. (1984) Increased transglutaminase activity in elicited and activated macrophages: Relationship to production of superoxide anion.
J. Leukocyte Biol., 36, 719-727.
31. Suzuki, H., Pabst, M.J., and Johnston, R.B., Jr. (1985) Enhancement by Ca2+ or Mg2+ of catalytic activity of the superoxide-producing NADPH oxidase in membrane fractions of human neutrophils and monocytes. J. Biol. Chem., 260, 3634-3639.
35. Edwards, C.K., III, Hedegaard, H.B., Zlotnik, A., Gangadharam, P.R., Johnston, R.B., Jr., and Pabst, M.J. (1986) Chronic infection due to mycobacterium intracellulare in mice: Association with macrophage release of prostaglandin E2 and reversal by injection with indomethacin, muramyl dipeptide or interferon-g. J. Immunol.,136, 1820-1827.
36. Speer, C.P., Gahr, M., and Pabst, M.J. (1986) Phagocytosis-associated oxidative metabolism in human milk macrophages. Acta Pediatrica Scand. , 75, 444-451.
37. Bryant, S.M., Guthrie, L.A., Pabst, M.J., and Johnston, R.B., Jr. (1986) Macrophage membrane proteins: Possible role in the regulation of priming for enhanced respiratory burst activity. Cell. Immunol. 103, 216-223.
40. Finkel, T.H., Pabst, M.J., Suzuki, H., Guthrie, L.A., Forehand, J.R., Phillips, W.A., and Johnston, R.B., Jr. (1987) Priming of neutrophils and macrophages for enhanced release of superoxide anion by the calcium ionophore ionomycin. J. Biol. Chem., 262, 12589-12596.
41. Pabst, M.J., Gross, J.M., Brozna, J.P., and Goren, M.B. (1988) Inhibition of macrophage priming by sulfatide from mycobacterium tuberculosis. J. Immunol. 140, 634-640.
42. Mor, N., Goren M.B. and Pabst, M.J. (1988) Mycobacterium lepraemurium activates macrophages but fails to trigger release of superoxide anion. J. Immunol., 140, 3956-3961.
43. Forehand, J.R., Pabst, M.J., Phillips, W.A., and Johnston, R.B., Jr. (1989) Lipopolysaccharide priming of human neutrophils for an enhanced respiratory burst: Role of intracellular free calcium. J. Clin. Invest. 83, 74-83.
44. Szefler, S.J., Norton, C.E., Ball, B., Gross, J. M., Aida, Y., and Pabst, M.J. (1989) IFN-g and LPS overcome glucocorticoid inhibition of priming for superoxide release in human monocytes: Evidence that secretion of IL-1 and TNFa is not essential for monocyte priming. J. Immunol., 142, 3985-3992.
47. Wright, S.D., Detmers, P.A., Aida, Y., Adamowski, R., Anderson, D.C., Chad, Z., Kabbash, L.G., and Pabst, M.J. (1990) CD18-deficient cells respond to lipopolysaccharide in vitro.
J. Immunol., 144, 2566-2571.
48. Aida, Y. and Pabst, M.J. (1990) Removal of endotoxin from protein solutions by phase separation using Triton X-114. J. Immunol. Methods, 132, 191-195.
49. Aida, Y. and Pabst, M.J. (1990) Priming of neutrophils by lipopolysaccharide for enhanced release of superoxide. Requirement for plasma but not for tumor necrosis factor-a. J. Immunol., 145, 3017-3025.
50. Aida, Y. and Pabst, M.J. (1991) Neutrophil responses to lipopolysaccharide: Effect of adherence on triggering and priming of the respiratory burst. J. Immunol., 146, 1271-1276.
51. Brozna, J.P., Horan, M., Rodemacher, J.M., Pabst, K.M., and Pabst, M.J. (1991) Monocyte responses to sulfatide from mycobacterium tuberculosis: Inhibition of priming for enhanced release of superoxide, associated with increased secretion of interleukin-1 and tumor necrosis factor alpha, and altered protein phosphorylation. Infect. Immun., 59, 2542-2548.
59.Wang, D., Pabst, K.M., Aida, U., and Pabst, M.J. (1995) Lipopolysaccharide inactivating activity of neutrophils is due to lactoferrin. J. Leukoc. Biol., 57, 865-874.
60.Aida, Y., Kukita, T., Takada, H., Maeda, K., and Pabst, M.J. (1995) Lipopolysaccharides from periodontal pathogens prime neutrophils for enhanced respiratory bust: Differential effect of a synthetic lipid a precusor IVA (LA-14-PP). J. Periodont. Res., 30, 116-123.