Peter Henson
Professor
Ph.D., University of Cambridge, 1967

Cell Biology of inflammation, innate immunity and apoptotic cell removal.

Our group has four major, interacting areas of interest. One focuses on the initiation, progression, resolution and mediator control of the inflammatory process, extending from the biochemical, molecular and cellular levels to animal systems and patient investigation.

A second focus is represented by our interest in apoptosis, and particularly the role of apoptotic cell recognition (by mononuclear phagocytes, dendritic cells and near neighbor tissue cells) in tissue homeostasis (cell removal and replacement), tissue remodeling, as well as resolution and suppression of inflammation and adaptive immunity.

A unique form of phagocytosis appears responsible for apoptotic cell removal from tissues. We have named this "efferocytosis" (from "effero" - to carry to the grave, to bury). It is highly conserved within all metazoa, significantly precedes (in evolutionary terms) "classic" phagocytosis driven by Fc receptor ligation and can be carried out to various levels of efficiency in most mammalian cell types. Signaling, mechanisms, consequences and relation to innate immunity represent an additional focus.

Innate immunity is mediated by groups of soluble or cell surface ligands for pathogen associated molecular patterns (PAMPs). It is now apparent that recognition of apoptotic and necrotic cells shows significant similarities and consequences resulting in a delicate balance between anti- and pro-inflammatory responses and subsequent adaptive immunity. Regulation of mononuclear phagocyte participation in adaptive immune responses to host and parasite is a third interest in our research group.

Recent Publications:

  1. Fadok VA, Bratton DL, Rose D, Pearson A, Ezekowitz A, Henson PM. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405:85-90, 2000.
  2. Yujuri T, Ware M, Widmann C, Oyer R, Russell D, Chan E, Zaitsu Y, Clarke P, Tyler K, Oka Y, Fanger GR, Henson P, Johnson GL. MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NFkB activation. Proc. Natl. Acad. Sci. USA 97(13):7272-7277, 2000.
  3. Whitlock BB, Gardai S, Fadok V, Bratton D, Henson PM. Differential roles for amb2 integrin clustering or activation in the control of apoptosis via regulation of Akt and ERK survival mechanisms. J Cell Biol. 141:1305-1320, 2000.
  4. Taylor PR, Carugati A, Fadok VA, Cook HT, Andrews M, Carroll MC, Savill JS, Henson PM, Botto M, Walport MJ. A heirarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo: a mechanism for protection from autoimmunity. J Exp Med. 192:359-366, 2000.
  5. Frasch SC, Henson PM, Kailey JM, Richter DA, Janes MS, Fadok VA, Bratton DL. Regulation of phospholipid scramblase activity during cell activation and apoptosis by PKCd. J. Biol. Chem. 275:23065-23073, 2000.
  6. Bowers RC, Hevko J, Henson PM, Murphy RC. A novel glutathione containing eicosanoid (FOG7) chemotactic for human granulocytes. J Biol Chem 275(39):29931-29934, 2000.
  7. Fadok VA, de Cathelineau A, Henson PM, Bratton DL. Loss of phospholipid asymmetry and surface exposure of phosphatidylserine is required for phagocytosis of apoptotic cells by macrophages and fibroblasts. J. Biol. Chem. 276(2):1071-1077, 2001.
  8. Ogden CA, deCathelineau A, Hoffmann PR, Fadok VA, Bratton D, Henson PM. C1q and collectin engagement of cell surface calreticulin initiates macropinocytosis and uptake of apoptotic cells. J. Exp. Med. 194(6):781-795, 2001.
  9. Fadok VA, Bratton DL, Henson PM. Phagocyte receptors for apoptotic cells: recognition, uptake and consequences. J. Clin Invest. 108:957-962, 2001.
  10. Hoffmann PR, deCathelineau AM, Ogden CA, Leverrier Y, Bratton DL, Daleke DL, Ridley AJ, Fadok VA, Henson PM. Phosphatidylserine (PS) induces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells. J Cell Biol 155(4):649-659, 2001.
  11. Riches DWH, Henson PM. Pulmonary macrophages: origins, functions and clearance. In: Basic mechanisms of pediatric respiratory disease.2nd ed.Haddad GG, Abman SH, Chernick V, eds. BC Decker, Hamilton, Ontario, Chapter 36, pp 489-504, 2002.
  12. Huynh, M-LN, Fadok VA, Henson PM. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGFb1 secretion and resolution of inflammation. J Clin Invest 109:41-50, 2002.
  13. Gardai S, Whitlock BB, Helgason C, Ambruso D, Fadok V, Bratton D, Henson PM. Activation of SHIP by NADPH oxidase stimulated Lyn leads to enhanced apoptosis in neutrophils. J Biol Chem. 277:5236-5246, 2002.
  14. Vandivier RW, Fadok VA, Hoffmann PR, Bratton DL, Penvari C, Brown KK, Brain JD, Accurso FJ, Henson PM. Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis. J Clin Invest. 109:661-670, 2002.
  15. Xiao YQ, Malcolm K, Worthen GS, Gardai S, Schiemann WP, Fadok VA, Bratton D, Henson PM. Cross talk between ERK and p38 MAPK mediates selective suppression of pro-inflammatory cytokines by TGF-b. J Biol Chem 277(17):14884-14893, 2002.
  16. Teder P, Vandivier RW, Jiang D, Liang J, Pure E, Henson PM, Noble PW. Resolution of lung inflammation by CD44. Science 296(5565):155-158, 2002.
  17. Nick JA, Young SK, Arndt PG, Lieber JG, Suratt BT, Poch KR, Avdi NJ, Malcolm KC, Taube C, Henson PM, Worthen GS. Selective suppression of neutrophil accumulation in ongoing pulmonary inflammation by systemic inhibition of p38 mitogen-activated protein kinase. J Immunol 169:5260-5269, 2002.
  18. Vandivier RW, Ogden CA, Fadok VA, Hoffmann PR, Brown KK, Botto M, Walport MJ, Fisher JH, Henson PM, Greene KE. Role of surfactant proteins a, d, and c1q in the clearance of apoptotic cells in vivo and in vitro: Calreticulin and CD91 as a common collectin receptor complex. J Immunol 169:3978-3986, 2002.
  19. Wang Y, Yi-Chun Wu Y-C, Valerie A. Fadok VA, Lee M-C, Gengyo-Ando K, Cheng L-C, Ledwich D, Hsu P-K, Henson P, Mitani S and Xue D. C. elegans Phosphatidylserine receptor acts through CED-5/CED-12 to mediate cell corpse engulfment. Science, 2003, In Press
  20. deCathelineau AM, Henson PM. Efferocytosis is the final step in apoptosis. In: Essays in Biochemistry, ed. Cotter T. 2003 In Press
  21. Gardai SH, Xiao Y-Q, Dickinson M, Nick J, Voelker D, Greene K, Henson P. By binding SIRPa or calreticulin/CD91, lung collectins act as dual function surveillance molecules to either suppress or enhance inflammation. Cell. In Press 2003.

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