|Areas of Expertise|
Specific cells in the body are designed to ingest dangerous particles, such as invading bacteria. These professional eating cells, or phagocytes, also eat dead or dying cells. This process of clearance of dead or dying cells is necessary to allow for the repair of damaged tissue, and to maintain normal tissue. When this process of cellular ingestion (phagocytosis) is dysregulated, the body becomes susceptible to chronic infections and autoimmunity. My laboratory focuses on phagocyte recognition and clearance events with the goal of developing therapies that strengthen the body’s ability to ingest and kill infectious particles or dead/dying cells.
Billions of cells die in the body every day by normal processes (apoptosis). These dead cells need to be recognized by phagocytes and cleared rapidly. C1q is a protein that regulates phagocytosis of dead cells. It is found in blood and expressed in response to inflammatory signals. C1q may be used by the body to modulate the response to injury and to decrease the damage associated with inflammation. We are testing C1q and related molecules called “defense collagens” for their ability to regulate these events. These studies may help develop novel therapeutics to fight inflammatory and autoimmune diseases such as atherosclerosis, rheumatoid arthritis and lupus.
Figure. Phagocytic cells must functionally sum the signals received from the particles being detected via their diverse pattern recognition receptors to direct a gene expression program that dictates an appropriate immune response (inflammatory or anti-inflammatory). TF, transcription factor; TLR, Toll like receptor, PSR; phosphatidyl serine receptor; C1qR, C1q/MBL receptor. Artwork by Cheryl Cotman. Reproduced from Bohlson et al., 2006, Molecular Immunology (www.elsevier.com/locate/molimm).
Hulsebus, H.J., O’Conner, SD., Smith, E.M., Jie, C., and Bohlson, S.S. Programmed efferocytosis and inhibition of proinflammatory signaling by complement component C1q in primary macrophages.” Frontiers in Immunology. 2016.
Bohlson, SS. Phagocytosis. Encyclopedia of Molecular Life Sciences. Springer, 2015.
Foreman, D.B. and Bohlson, S.S. Innate Immunity. Encyclopedia of Molecular Life Sciences. Springer 2014.
Galvan, M. D., Hulsebus, H., Heitker, T., Zeng, E., and Bohlson, S.S.Complement protein C1q and adiponectin stimulate Mer tyrosine kinase dependent engulfment of apoptotic cells through a shared pathway. Journal of Innate Immun. 2014 Jun 17. [Epub ahead of print] PMID: 24942043
Bohlson, S.S., O’Conner, S.D., Hulsebus, H., Ho, M., and Fraser, D.A. Complement, C1q, and C1q-related molecules regulate macrophage polarization. Frontiers in Immunology, Aug 21, 2014.
Galvan, M.D., Foreman D.B., Zeng, E., Tan, J.C., Bohlson, S.S. Complement component C1q regulates macrophage expression of Mer tyrosine kinase to promote clearance of apoptotic cells, Journal of Immunology. 188(8):3716-23. Apr 15, 2012
Galvan MD, Greenlee-Wacker MC, and Bohlson, S.S. C1q and phagocytosis: the perfect complement to a good meal. Journal of Leukocyte Biology. 92(3):489-97. Sep, 2012
Greenlee-Wacker MC, Briseño C, Galvan M, Moriel G, Velázquez P, Bohlson, S.S. Membrane-Associated CD93 Regulates Leukocyte Migration and C1q-Hemolytic Activity during Murine Peritonitis. Journal of Immunology. 2011, Sep 15;187(6):3353-61. Epub Aug 17., 2011
Greenlee-Wacker MC, Galvan MD and Bohlson, S.S. CD93: Recent Advances and Implications in Disease. Current Drug Targets. [Epub ahead of print]. Dec 29, 2011
Kozmar, A., Greenlee-Wacker, M.C., Bohlson, S.S. Macrophage response to apoptotic cells varies with the apoptotic trigger and is not altered by a deficiency in LRP expression. Journal of Innate Immunity. 2(3): 248- 259., 2010
Greenlee, M., Sullivan, S., and Bohlson, S.S. Detection and characterization of soluble CD93 released during inflammation. Inflammation Research, July 15 , 2009
Greenlee, M.C., Sullivan, S.A., and Bohlson, S.S. CD93 and Related Family Members: Their Role in Innate Immunity. Review. Current Drug Targets. (2):130-8. Feb 9, 2008
Lillis, A., Greenlee, M., Mikhailenko, I., Pizzo S., Tenner A., Strickland, D., and Bohlson, S. Murine LRP is required for phagocytosis of targets bearing LRP ligands but is not required for C1q-triggered enhancement of phagocytosis. Journal of Immunology. 181(1): 364-373. July, 2008
Fraser, D., Arora, M., Bohlson, S.S, Lozano, E., and Tenner, A.J. Generation of Inhibitory NFκB Complexes and pCREB Correlates with the Anti-inflammatory Activity of Complement Protein C1q in Human Monocytes. J Biol Chem. 282(10):7360-7. Mar 9, 2007
Bohlson, S.S., Fraser, D., Tenner, A.J. Complement Proteins C1q and MBL are Pattern Recognition Molecules that Signal Immediate and Long Term Protective Immune Functions. Review. Molecular Immunology. 44(1-3):33-43. Jan, 2007
Fraser D., Bohlson, S.S, Jasinskiene, N., Rawal, N., Palmerini, G., Ruiz, S., Rochford, R., and Tenner, A. C1q and MBL, components of the innate immune system, modulate monocyte cytokine expression. Journal of Leukocyte Biology; 80(1):107-16. Jul, 2006
Bohlson, S.S., Silva, R. Fonseca, M.I. and Tenner, A.J. CD93 is rapidly shed from the surface of human myeloid cells in response to a variety of stimuli and the soluble form is detected in human plasma. Journal of Immunology, 175: 1239-1247., 2005
Zhang, M., Bohlson, S.S., Dy, M., and Tenner, A.J. Modulated interaction of the ERM protein, moesin, with CD93. Immunology, 115:63-73., 2005
Bohlson, S.S, Zhang, M., Ortiz, C.E., and Tenner, A.J. CD93 interacts with the PDZ doman containing protein GIPC: Implications in the modulation of phagocytosis. Journal of Leukocyte Biology, 77(1):80-9., 2005
Bohlson, S.S., Strasser, J.A., Bower, J.J and Schorey J.S.: The Role of Complement in M. avium Pathogenesis: In vitro and in vivo analysis of the Host Response in the Absence of Complement Component C3. Infection and Immunity, 69 (12) 7729-35., 2001
Blystone, S.D., Slater, S.E., Williams, M.P., Crow, M.T. and Brown, E.J.: A Molecular Mechanism of Integrin Crosstalk: αvβ3 Supression of Calcium/Calmodulin-Dependent Protein Kinase II Regulates α5β1 Function. Journal of Cell Biology, 145 (4):889-897, 1999
Roach, T.I.A., Slater, S.E., White, L., Zhang, X., Majerus, P.W., Brown, E.J., and Thomas, M.L.: The Protein Tyrosine Phosphatase SHP-1 Regulates Integrin-mediated Adhesion of Macrophages. Current Biology, 8(18):1035-1038, 1998
Blystone, S.D., Williams, M.P., Slater, S.E., and Brown, E.J.: Requirement of Integrin β3 Tyrosine 747 for β3 Tyrosine Phosphorylation and Regulation of αvβ3 Avididty. Journal of Biological Chemistry, 272 (45): 28757-28761, 1997
Roach, T.I.A., Slater, S.E., Koval, M., White, L., Cahir McFarland, E., Okumura, M., Thomas, M., and Brown, E.J. CD45 Regulates Src Family Kinase Activity associated with Macrophage Integrin-mediated Adhesion. Current Biology, 7(6):408-417, 1997
Thomas, M.L., Roach, T.I.A., Slater, S.E., White, L., Okumura, M., and Brown, E.J.: The Protein Tyrosine Phosphatase, CD45, in Adhesion and Signal Transduction. Kinases and Phosphatases in Lymphocyte and Neuronal Signaling. New York: Springer-Verlag, 1997