Department of Microbiology and Immunology
Carl Atkinson, PhD
2004 – 2006 Post Doctoral Fellow, CRI , Medical University of South Carolina
2004 PhD, University of the West of England, Bristol, England
Heart transplantation is an accept treatment modality for patients with end-stage heart disease. These patients have reached the end of conventional pharmacological therapy or surgical interventions and the only therapeutic option left is heart transplantation. Current first year survival rates post transplantation varies between 80-95%, and patients surviving beyond the first can expect an average half-life of 11 years. While these results are acceptable patients eventually succumb to chronic rejection which manifests as an obliterative vascular lesion which restricts the hearts blood supply and eventually leads to heart failure. The precise mechanisms that contribute to the development of chronic rejection are unknown, but recent data implicates the early ischemic damage these hearts receive due to the transplant process and brain death.
Results from kidney transplantation have shown that the quality of the donor organ is important for post transplant survival. Organs donated from living donors perform better than those harvested from cadaveric donors. It is believed that the processes stimulated during brain death in these cadaveric donors, activates the donor heart rendering it more susceptible to ischemic damage, upon implantation, and ultimately acute and chronic rejection. The mechanisms responsible for these inflammatory changes to the donor organ are poorly characterized. Our research focuses on the elucidation of these mechanisms and the application of novel therapies that can be applied to the donor prior to transplantation to limit donor organ damage. During brain death all of the organs in the body are exposed to ischemia and chaotic changes in blood supply and pressure. Our studies have implicated the complement system in the activation of the donor heart. The complement system is composed of a series of serum proteins that work in a concerted fashion to induce cell death, promote inflammation and pro-inflammatory cytokines. We have been working with complement inhibitory proteins with the aim to reduce complement mediated brain death induced inflammation and ultimately to reduce the incidence and severity of both acute and chronic rejection.
Recent Publications | Additional Publications
Ellett JD, Atkinson C, Evans ZP, Amani Z, Balish E, Schmidt MG, van Rooijen N, Schnellmann RG, Chavin KD. Murine Kupffer cells are protective in total hepatic ischemia/reperfusion injury with bowel congestion through IL-10. J Immunol 2010 May 15;184(10):5849-58. Epub 2010 Apr 16. PubMed PMID: 20400698.
He S, Atkinson C, Qiao F, Chen X, Tomlinson S. Ketamine-Xylazine-Acepromazine Compared with Isoflurane for Anesthesia during Liver Transplantation in Rodents. J Am Assoc Lab Anim Sci 2010;49(1):45-51. PubMed PMID: 20122316; PubMed Central PMCID: PMC2824967.
Davis KS, Casey SE, Mulligan JK, Mulligan RM, Schlosser RJ, Atkinson C. Murine complement deficiency ameliorates acute cigarette smoke-induced nasal damage. Otolaryngol Head Neck Surg 2010;143(1):152-8.
Schlosser RJ, Mulligan RM, Casey SE, Varela JC, Harvey RJ, Atkinson C. Alterations in gene expression of complement components in chronic rhinosinusitis. Am J Rhinol Allergy 2010;24(1):21-5.
Mulligan RM, Atkinson C, Vertegel AA, Reukov V, Schlosser RJ. Cigarette smoke extract stimulates interleukin-8 production in human airway epithelium and is attenuated by superoxide dismutase in vitro. Am J Rhinol Allergy 2009;23(6):e1-4.
Atkinson C, Varela JC, Tomlinson S. Complement-dependent inflammation and injury in a murine model of brain dead donor hearts. Circ Res 2009 Nov 20;105(11):1094-101. Epub 2009 Oct 8. PubMed PMID: 19815824; PubMed Central PMCID: PMC2783176.
He S, Atkinson C, Evans Z, Ellett JD, Southwood M, Elvington A, Chavin KD, Tomlinson S. A role for complement in the enhanced susceptibility of steatotic livers to ischemia and reperfusion injury. J Immunol 2009;Oct 1;183(7):4764-72. Epub 2009 Sep 14. PubMed PMID: 19752222.
Ellett JD, Evans ZP, Atkinson C, Schmidt MG, Schnellmann RG, Chavin KD. Toll-like receptor 4 is a key mediator of murine steatotic liver warm ischemia/reperfusion injury. Liver Transpl 2009;15(9):1101-9. PMCID: 2938042.
Southwood M, Jeffery TK, Yang X, Upton PD, Hall SM, Atkinson C, et al. Regulation of bone morphogenetic protein signalling in human pulmonary vascular development. J Pathol 2008;214(1):85-95.
Atkinson C, Qiao F, Song H, Gilkeson GS, Tomlinson S. Low-dose targeted complement inhibition protects against renal disease and other manifestations of autoimmune disease in MRL/lpr mice. J Immunol 2008;180(2):1231-8.
Atkinson C, Zhu H, Qiao F, Varela JC, Yu J, Song H, et al. Complement-dependent P-selectin expression and injury following ischemic stroke. J Immunol 2006;177(10):7266-74.
Mahadeva R, Atkinson C, Li Z, Stewart S, Janciauskiene S, Kelley DG, et al. Polymers of Z alpha1-antitrypsin co-localize with neutrophils in emphysematous alveoli and are chemotactic in vivo. Am J Pathol 2005;166(2):377-86.
Atkinson C, Southwood M, Pitman R, Phillpotts C, Wallwork J, Goddard M. Angiogenesis occurs within the intimal proliferation that characterizes transplant coronary artery vasculopathy. J Heart Lung Transplant 2005;24(5):551-8.
Atkinson C, Song H, Lu B, Qiao F, Burns TA, Holers VM, et al. Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection. J Clin Invest 2005;115(9):2444-53.
Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, et al. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 2002;105(14):1672-8.
Title: Nanoparticle coupled therapeutics to inhibit smoke-induced oxidative inflammation in allergic rhinitis
Agency: South Carolina Clinical Translational Research Institute
Funding Period: 10/01/2009 - 02/28/2011
Title: The role of complement in the pathogenesis of emphysema
Funding Period: 03/01/2010 - 02/28/2011
Title: The role of complement in second hand smoke exacerbation of asthma
Agency: Flight Association Medical Research Institute
Funding Period: 07/01/2010 – 06/30/2013
Title: Nanoparticle therapy of lung cancer
Agency: Department of Defense
Funding Period: 09/01/2010 – 08/30/2011
Title: Complement activation age related macular degeneration
Agency: VA Merit
Funding Period: 10/01/2010 – 09/30/2014