It has been an honor for me to write the prefatory article for Volume 4 of the . I decided to describe the first 50 years of my career in research, which started with my entry into medical school. I have tried to outline the numerous scientific mentors who played such an important role in my development as an independent scientific investigator. In general, I have tried to avoid mention in the text of the many, many colleagues who carried out the scientific work, as I would inevitably fail to cite many of them. Rather, I have cited what I think are my most important publications, which identify many of these scientific colleagues. I am now engaged nearly full-time in research and look forward to the next period of research progress.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Ward PA, Johnson AG. 1.  1959. Studies on the adjuvant action of bacterial endotoxins on antibody formation. II. Antibody formation in cortisone-treated rabbits. J. Immunol. 82:428–34 [Google Scholar]
  2. Ward PA, Johnson AG, Abell MR. 2.  1959. Studies on the adjuvant action of bacterial endotoxins on antibody formation. III. Histologic response of the rabbit spleen to a single injection of a purified protein antigen. J. Exp. Med. 109:463–74 [Google Scholar]
  3. Ward PA, Abell MR, Johnson AG. 3.  1961. Studies on the adjuvant action of bacterial endotoxins on antibody formation. IV. Histologic study of cortisone-treated rabbits. Am. J. Pathol. 38:189–205 [Google Scholar]
  4. Ward PA, Cochrane CG. 4.  1965. Bound complement and immunologic injury of blood vessels. J. Exp. Med. 121:215–34 [Google Scholar]
  5. Ward PA, Cochrane CG, Muller-Eberhard HJ. 5.  1965. The role of serum complement in chemotaxis of leukocytes in vitro. J. Exp. Med. 122:327–46 [Google Scholar]
  6. Ward PA, Cochrane CG, Muller-Eberhard HJ. 6.  1966. Further studies on the chemotactic factor of complement and its formation in vivo. Immunology 11:141–53 [Google Scholar]
  7. Ward PA. 7.  1966. The chemosuppression of chemotaxis. J. Exp. Med. 124:209–26 [Google Scholar]
  8. Becker EL, Ward PA. 8.  1967. Partial biochemical characterization of the activated esterase required in the complement-dependent chemotaxis of rabbit polymorphonuclear leukocytes. J. Exp. Med. 125:1021–30 [Google Scholar]
  9. Ward PA, Becker EL. 9.  1967. Mechanisms of the inhibition of chemotaxis by phosphonate esters. J. Exp. Med. 125:1001–20 [Google Scholar]
  10. Ward PA, Becker EL. 10.  1968. The deactivation of rabbit neutrophils by chemotactic factor and the nature of activatable esterase. J. Exp. Med. 127:693–709 [Google Scholar]
  11. Becker EL, Ward PA. 11.  1969. Esterases of the polymorphonuclear leukocyte capable of hydrolyzing acetyl DL-phenyl-alanine β-naphthyl ester: relationship to the activatable esterase of chemotaxis. J. Exp. Med. 129:569–84 [Google Scholar]
  12. Ward PA, Becker EL. 12.  1970. Biochemical demonstration of the activatable esterase of the rabbit neutrophil involved in the chemotactic response. J. Immunol. 105:1057–67 [Google Scholar]
  13. Taylor FB Jr, Ward PA. 13.  1967. Generation of chemotactic activity in rabbit serum by plasminogen-streptokinase mixtures. J. Exp. Med. 126:149–58 [Google Scholar]
  14. Ward PA, Lepow IH, Newman LJ. 14.  1968. Bacterial factors chemotactic for polymorphonuclear leukocytes. Am. J. Pathol. 52:725–36 [Google Scholar]
  15. Ward PA, Schlegel RA. 15.  1969. Impaired leukotactic responsiveness in a child with recurrent infections. Lancet 2:344–47 [Google Scholar]
  16. Ward PA, Newman LJ. 16.  1969. A neutrophil chemotactic factor from human C′5. J. Immunol. 102:93–99 [Google Scholar]
  17. Ward PA, Hill JH. 17.  1970. C5 chemotactic fragments produced by an enzyme in lysosomal granules of neutrophils. J. Immunol. 104:535–43 [Google Scholar]
  18. Ward PA, Remold HG, David JR. 18.  1969. Leukotactic factor produced by sensitized lymphocytes. Science 163:1079–81 [Google Scholar]
  19. Ward PA, Remold HG, David JR. 19.  1970. The production by antigen-stimulated lymphocytes of a leukotactic factor distinct from migration inhibitory factor. Cell. Immunol. 1:162–74 [Google Scholar]
  20. Remold HG, Ward PA, David JR. 20.  1971. Characterization of migration inhibitor factor (MIF) and its separation from a chemotactic factor for monocytes. Int. Arch. Allerg. Appl. Immunol. 41:16–17 [Google Scholar]
  21. Schiffmann E, Showell H, Corcoran B, Ward PA, Smith E, Becker EL. 21.  1975. The isolation of partial characterization of neutrophil chemotactic factors from Escherichia coli. J. Immunol. 114:1831–37 [Google Scholar]
  22. Ward PA, Zvaifler NJ. 22.  1971. Complement-derived leukotactic factors in inflammatory synovial fluids of humans. J. Clin. Invest. 50:606–16 [Google Scholar]
  23. Ward PA, Ozols J. 23.  1976. Characterization of the protease activity in the chemotactic factor inactivator. J. Clin. Invest. 58:123–29 [Google Scholar]
  24. Brozna JP, Senior RM, Kreutzer DL, Ward PA. 24.  1977. Chemotactic factor inactivator of human granulocytes. J. Clin. Invest. 60:1280–88 [Google Scholar]
  25. Muhlfelder TW, Niemetz J, Kreutzer D, Beebe D, Ward PA, Rosenfeld SI. 25.  1979. C5 chemotactic fragment induces leukocyte production of tissue factor activity: a link between complement and coagulation. J. Clin. Invest. 63:147–50 [Google Scholar]
  26. Romualdez AG Jr, Ward PA. 26.  1975. A unique complement-derived chemotactic factor for tumor cells. Proc. Natl. Acad. Sci. USA 72:4128–32 [Google Scholar]
  27. Romualdez AG Jr, Ward PA, Torikata T. 27.  1976. Relationship between the C5 peptides chemotactic for leukocytes and tumor cells. J. Immunol. 117:1762–66 [Google Scholar]
  28. Orr W, Varani J, Ward PA. 28.  1978. Characteristics of the chemotactic response of neoplastic cells to a factor derived from the fifth component of complement. Am. J. Pathol. 93:405–22 [Google Scholar]
  29. Lam WC, Delikatny J, Orr W, Wass J, Varani J, Ward PA. 29.  1981. Chemotactic response of tumor cells: a model for cancer metastases. Am. J. Pathol. 104:69–76 [Google Scholar]
  30. Orr FW, Varani J, Kreutzer DL, Senior RM, Ward PA. 30.  1979. Digestion of the fifth component of complement by leukocyte enzymes: sequential generation of chemotactic activities for leukocytes and for tumor cells. Am. J. Pathol. 94:75–83 [Google Scholar]
  31. Orr W, Phan SH, Varani J, Ward PA, Kreutzer DL. 31.  et al. 1979. Chemotactic factor for tumor cells derived from the C5 fragment of complement component C5. Proc. Natl. Acad. Sci. 76:1986–89 [Google Scholar]
  32. Marasco WA, Fantone JC, Ward PA. 32.  1982. Spasmogenic activity of chemotactic N-formylated oligopeptides: identity of structure-function relationships for chemotactic and spasmogenic activities. Proc. Natl. Acad. Sci. USA 79:7470–73 [Google Scholar]
  33. Marasco WA, Fantone JC, Freer RJ, Ward PA. 33.  1983. Characterization of the rat neutrophil formyl peptide chemotaxis receptor. Am. J. Pathol. 111:273–81 [Google Scholar]
  34. Marasco WA, Phan SH, Krutzsch H, Showell HJ, Feltner DE. 34.  et al. 1984. Purification and identification of formyl-methionyl-leucyl-phenylalanine as the major peptide neutrophil chemotactic factor produced by Escherichia coli. J. Biol. Chem. 259:5430–39 [Google Scholar]
  35. Marasco WA, Feltner DE, Ward PA. 35.  1985. Formyl peptide chemotaxis receptors on the rat neutrophil: experimental evidence for negative cooperativity. J. Cell Biochem. 27:359–75 [Google Scholar]
  36. Johnson KJ, Fantone JC III, Kaplan J, Ward PA. 36.  1981. In vivo damage of rat lungs by oxygen metabolites. J. Clin. Invest. 67:983–93 [Google Scholar]
  37. Johnson KJ, Ward PA. 37.  1981. Role of oxygen metabolites in immune complex injury of lung. J. Immunol. 126:2365–69 [Google Scholar]
  38. Fantone JC, Ward PA. 38.  1982. Review article: role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am. J. Pathol. 107:395–418 [Google Scholar]
  39. Ward PA, Till GO, Kunkel R, Beauchamp C. 39.  1983. Evidence for role of hydroxyl radical in complement and neutrophil-dependent tissue injury. J. Clin. Invest. 72:789–801 [Google Scholar]
  40. McCormick JR, Harkin MM, Johnson KJ, Ward PA. 40.  1981. Suppression by superoxide dismutase of immune-complex-induced pulmonary alveolitis and dermal inflammation. Am. J. Pathol. 102:55–61 [Google Scholar]
  41. Strieter RM, Kunkel SL, Showell HJ, Remick DG, Phan SH. 41.  et al. 1989. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-α, LPS, and IL-1β. Science 243:1467–69 [Google Scholar]
  42. Kilgore KS, Schmid E, Shanley TP, Flory CM, Maheswari V. 42.  et al. 1997. Sublytic concentrations of the membrane attack complex (MAC) of complement induce endothelial interleukin 8 (IL-8) and monocyte protein 1 (MCP-1) through nuclear factor–kappa B (NF-κB) activation. Am. J. Pathol. 150:2019–31 [Google Scholar]
  43. Riedemann NC, Guo RF, Sarma VJ, Laudes IJ, Huber-Lang M. 43.  et al. 2002. Expression and function of the C5a receptor in rat alveolar epithelial cells. J. Immunol. 168:1919–25 [Google Scholar]
  44. Marks RM, Todd RF III, Ward PA. 44.  1989. Rapid induction of neutrophil-endothelial adhesion by endothelial complement fixation. Nature 339:314–17 [Google Scholar]
  45. Mulligan MS, Schmid E, Beck-Schimmer B, Till GO, Friedl HP. 45.  et al. 1996. Requirement and role of C5a in acute lung inflammatory injury in rats. J. Clin. Invest. 98:503–12 [Google Scholar]
  46. Czermak BJ, Lentsch AB, Bless NM, Schmal H, Friedl HP, Ward PA. 46.  1998. Role of complement in in vitro and in vivo lung inflammatory reactions. J Leukoc. Biol. 64:40–48 [Google Scholar]
  47. Shanley TP, Schmal H, Friedl HP, Jones ML, Ward PA. 47.  1995. Role of macrophage inflammatory protein-1α (MIP-1α) in acute lung injury in rats. J. Immunol. 154:4793–802 [Google Scholar]
  48. Warren JS, Yabroff KR, Remick DG, Kunkel SL, Chensue SW. 48.  et al. 1989. Tumor necrosis factor participates in the pathogenesis of acute immune complex alveolitis in the rat. J. Clin. Invest. 84:1873–82 [Google Scholar]
  49. Bless NM, Huber-Lang M, Guo RF, Warner RL, Schmal H. 49.  et al. 2000. Role of CC chemokines (MIP-1β, MCP-1, RANTES) in acute lung injury in rats. J. Immunol. 164:2650–59 [Google Scholar]
  50. Mulligan MS, Varani J, Dame MK, Lane CL, Smith CW. 50.  et al. 1991. Role of endothelial-leukocyte adhesion molecule 1 (ELAM-1) in neutrophil-mediated lung injury in rats. J. Clin. Invest. 88:1396–406 [Google Scholar]
  51. Mulligan MS, Polley MJ, Bayer RJ, Nunn MF, Paulson JC, Ward PA. 51.  1992. Neutrophil-dependent acute lung injury: requirement for P-selectin (GMP-140). J. Clin. Invest. 90:1600–7 [Google Scholar]
  52. Mulligan MS, Varani J, Warren JS, Till GO, Smith CW. 52.  et al. 1992. Roles of β2 integrins of rat neutrophils in complement- and oxygen radical–mediated acute inflammatory injury. J. Immunol. 148:1847–57 [Google Scholar]
  53. Mulligan MS, Vaporciyan AA, Miyasaka M, Tamatani T, Ward PA. 53.  1993. Tumor necrosis factor α regulates in vivo intrapulmonary expression of ICAM-1. Am. J. Pathol. 142:1739–49 [Google Scholar]
  54. Vaporciyan AA, DeLisser HM, Yan H-C, Mendiguren II, Thom SR. 54.  et al. 1993. Involvement of platelet–endothelial cell adhesion molecule–1 in neutrophil recruitment in vivo. Science 262:1580–82 [Google Scholar]
  55. Foreman KE, Vaporciyan AA, Bonish BK, Jones ML, Johnson KJ. 55.  et al. 1994. C5a-induced expression of P-selectin in endothelial cells. J. Clin. Invest. 94:1147–55 [Google Scholar]
  56. Mulligan MS, Vaporciyan AA, Warner RL, Jones ML, Foreman KE. 56.  et al. 1995. Compartmentalized roles for leukocytic adhesion molecules in lung inflammatory injury. J. Immunol. 154:1350–63 [Google Scholar]
  57. Mulligan MS, Paulson JC, De Frees S, Zheng Z-L, Lowe JB, Ward PA. 57.  1993. Protective effects of oligosaccharides in P-selectin-dependent lung injury. Nature 364:149–51 [Google Scholar]
  58. Mulligan MS, Lowe JB, Larsen RD, Paulson J, Zheng Z-L. 58.  et al. 1993. Protective effects of sialylated oligosaccharides in immune complex–induced acute lung injury. J. Exp. Med. 178:623–31 [Google Scholar]
  59. Shanley TP, Foreback JL, Remick DG, Ulich TR, Kunkel SL, Ward PA. 59.  1997. Regulatory effects of IL-6 in IgG immune complex–induced lung injury. Am. J. Pathol. 151:193–203 [Google Scholar]
  60. Mulligan MS, Warner RL, Foreback JL, Shanley TP, Ward PA. 60.  1997. Protective effects of IL-4, IL-10, IL-12 and IL-13 in IgG immune complex–induced lung injury: role of endogenous IL-12. J. Immunol. 159:3483–89 [Google Scholar]
  61. Shanley TP, Peters JL, Jones ML, Chensue SW, Kunkel SL, Ward PA. 61.  1996. Regulatory effects of endogenous interleukin-1 receptor antagonist protein in IgG immune complex–induced lung injury. J. Clin. Invest. 97:963–70 [Google Scholar]
  62. Shanley TP, Schmal H, Friedl HP, Jones ML, Ward PA. 62.  1995. Regulatory effects of intrinsic IL-10 in IgG immune complex–induced lung injury. J. Immunol. 154:3454–60 [Google Scholar]
  63. Lentsch AB, Shanley TP, Sarma V, Ward PA. 63.  1997. In vivo suppression of NF-κB and preservation of IκBα by interleukin-10 and interleukin-13. J. Clin. Invest. 100:2443–244 [Google Scholar]
  64. Lentsch AB, Jordan JA, Czermak BJ, Diehl KM, Younkin EM. 64.  et al. 1999. Inhibition of NFκB activation and augmentation of IκBβ by secretory leukocyte protease inhibitor during lung inflammation. Am. J. Pathol. 154:239–47 [Google Scholar]
  65. Mulligan MS, Lentsch AB, Huber-Lang M, Guo RF, Sarma V. 65.  et al. 2000. Anti-inflammatory effects of mutant forms of secretory leukocyte protease inhibitor. Am. J. Pathol. 156:1033–39 [Google Scholar]
  66. Vaporciyan AA, Mulligan MS, Warren JS, Barton PA, Miyasaka M, Ward PA. 66.  1995. Upregulation of lung vascular ICAM-1 in rats is complement dependent. J. Immunol. 155:1442–49 [Google Scholar]
  67. Kilgore KS, Shen JP, Miller BF, Ward PA, Warren JS. 67.  1995. Enhancement by the complement membrane attack complex of tumor necrosis factor–α induced endothelial cell expression of E-selectin and ICAM-1. J. Immunol. 155:1434–41 [Google Scholar]
  68. Mulligan MS, Schmid E, Till GO, Hugli TE, Friedl HP. 68.  et al. 1997. C5a-dependent upregulation in vivo of lung vascular P-selectin. J. Immunol. 158:1857–61 [Google Scholar]
  69. Gao H, Guo RF, Speyer CL, Reuben J, Neff TA. 69.  et al. 2004. STAT3 activation in acute lung injury. J. Immunol. 172:7703–12 [Google Scholar]
  70. Huber-Lang M*, Sarma JV*, Zetoune FS*, Rittirsch D, Neff TA. 70.  et al. 2006. Generation of C5a in the absence of C3: a new complement activation pathway. Nat. Med. Lett. 12:682–87 *Authors contributed equally [Google Scholar]
  71. Flierl MA, Rittirsch D, Nadeau BA, Chen AJ, Sarma JV. 71.  et al. 2007. Phagocyte-derived catecholamines enhance acute inflammatory injury. Nat. Lett. 449:721–25 [Google Scholar]
  72. Guo RF, Huber-Lang M, Wang X, Sarma V, Padgaonkar VA. 72.  et al. 2000. Protective effects of anti-C5a in sepsis-induced thymocyte apoptosis. J. Clin. Invest. 106:1271–80 [Google Scholar]
  73. Chinnaiyan AM, Huber-Lang M, Kumar-Sinha C, Barrette TR, Shankar-Sinha S. 73.  et al. 2001. Molecular signatures of sepsis: multiorgan gene expression profiles of systemic inflammation. Am. J. Pathol. 159:1199–209 [Google Scholar]
  74. Riedemann NC, Guo RF, Ward PA. 74.  2003. Novel strategies for the treatment of sepsis. Nat. Med. 9:517–24 [Google Scholar]
  75. Riedemann NC, Guo RF, Ward PA. 75.  2003. The enigma of sepsis. J Clin. Invest. 112:460–67 [Google Scholar]
  76. Ward PA. 76.  2004. The dark side of C5a in sepsis. Nat. Rev. Immunol. 4:133–42 [Google Scholar]
  77. Huber-Lang M, Sarma VJ, Lu KT, McGuire SR, Padgaonkar BA. 77.  et al. 2001. Role of C5a in multi-organ failure during sepsis. J. Immunol. 166:1193–99 [Google Scholar]
  78. Huber-Lang MS, Riedemann NC, Sarma JV, Younkin EM, McGuire SR. 78.  et al. 2002. Protection of innate immunity by C5aR antagonist in septic mice. FASEB J. 16:1567–74 [Google Scholar]
  79. Riedemann NC, Neff TA, Guo RF, Bernacki KD, Laudes IJ. 79.  et al. 2003. Protective effects of IL-6 blockade in sepsis are linked to reduced C5a receptor expression. J. Immunol. 170:503–7 [Google Scholar]
  80. Laudes IJ, Chu JC, Sikranth S, Huber-Lang M, Guo RF. 80.  et al. 2002. Anti-C5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis. Am. J. Pathol. 160:1867–75 [Google Scholar]
  81. Guo RF, Riedemann NC, Bernacki KD, Sarma JV, Laudes IJ. 81.  et al. 2003. Neutrophil C5a receptor and the outcome in a rat model of sepsis. FASEB J. 17:1889–91 [Google Scholar]
  82. Huber-Lang MS, Sarma JV, McGuire SR, Lu KT, Guo RF. 82.  et al. 2001. Protective effects of anti-C5a peptide antibodies in experimental sepsis. FASEB J. 15:568–70 [Google Scholar]
  83. Czermak BJ, Sarma V, Pierson CL, Warner RL, Huber-Lang M. 83.  et al. 1999. Protective effects of C5a blockade in sepsis. Nat. Med. 5:788–92 [Google Scholar]
  84. Niederbichler AD, Hoesel LM, Westfall MV, Gao H, Ipaktchi KR. 84.  et al. 2005. An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction. J. Exp. Med. 203:53–61 [Google Scholar]
  85. Hoesel LM, Niederbichler AD, Ward PA. 85.  2007. Complement-related molecular events in sepsis leading to heart failure. Mol. Immunol. 44:95–102 [Google Scholar]
  86. Huber-Lang M*, Sarma JV*, Rittirsch D*, Schreiber H, Weiss M. 86.  et al. 2005. Changes in the novel orphan, C5a receptor (C5L2), during experimental sepsis and sepsis in humans. J. Immunol. 174:1104–10 *These authors contributed equally [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error