One of the major biological consequences of complement activation is the generation of three small cationic peptides C3a, C4a, and C5a, collectively referred to as complement anaphylatoxins. The complement anaphylatoxins are potent proinflammatory molecules that mediate numerous biological functions by binding to seven transmembrane G-protein coupled receptors expressed on specific target cells. The acute and chronic overproduction of complement anaphylatoxin peptides is considered to be a major contributor to the pathogenesis of numerous diseases, including rheumatoid arthritis, psoriasis, septic shock, myocardial ischemic injury, acute respiratory distress syndrome, and multiple system organ failure. The goal of this research program is to increase our understanding of the specific and overall roles that complement anaphylatoxin peptides and their receptors play in inflammation and immunity. During the next several years, the cellular expression and biological functions mediated by the C3a receptor will be examined in detail. In addition, the in vivo biological role of the C3a receptor will be studied and evaluated using a C3a receptor """"""""knock-out"""""""" mouse in several well-characterized models of inflammation, infection, and autoimmunity. These studies will be accomplished by four major specific aims: 1) to determine the cells in peripheral blood and selected tissues that express the C3a anaphylatoxin receptor, and to delineate C3a mediated biological functions by cells expressing the C3a receptor, 2) to determine the effect of C3a receptor deficiency on pulmonary inflammation in established models of immune-complex injury, asthma, and bacterial infection and clearance, 3) to determine the effect of C3a receptor deficiency in the skin using established models of infectious dermatitis, immune-complex injury, and bullous pemphigoid, and 4) to determine the effect of C3a receptor deficiency in the peritoneum using established models of immune-complex peritonitis, acute septic peritonitis, and septic shock.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Allergy and Immunology Study Section (ALY)
Program Officer
Sawyer, Richard T
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Health Science Center Houston
Schools of Medicine
United States
Zip Code
Mueller-Ortiz, Stacey L; Calame, Daniel G; Shenoi, Nancy et al. (2017) The Complement Anaphylatoxins C5a and C3a Suppress IFN-? Production in Response to Listeria monocytogenes by Inhibition of the Cyclic Dinucleotide-Activated Cytosolic Surveillance Pathway. J Immunol 198:3237-3244
Calame, Daniel G; Mueller-Ortiz, Stacey L; Wetsel, Rick A (2016) Innate and adaptive immunologic functions of complement in the host response to Listeria monocytogenes infection. Immunobiology 221:1407-1417
Hu, Xianzhen; Wetsel, Rick A; Ramos, Theresa N et al. (2014) Carboxypeptidase N-deficient mice present with polymorphic disease phenotypes on induction of experimental autoimmune encephalomyelitis. Immunobiology 219:104-8
Calame, Daniel G; Mueller-Ortiz, Stacey L; Morales, John E et al. (2014) The C5a anaphylatoxin receptor (C5aR1) protects against Listeria monocytogenes infection by inhibiting type 1 IFN expression. J Immunol 193:5099-107
Mueller-Ortiz, Stacey L; Morales, John E; Wetsel, Rick A (2014) The receptor for the complement C3a anaphylatoxin (C3aR) provides host protection against Listeria monocytogenes-induced apoptosis. J Immunol 193:1278-89
Dutow, Pavel; Fehlhaber, Beate; Bode, Jenny et al. (2014) The complement C3a receptor is critical in defense against Chlamydia psittaci in mouse lung infection and required for antibody and optimal T cell response. J Infect Dis 209:1269-78
Darley, M M; Ramos, T N; Wetsel, R A et al. (2012) Deletion of carboxypeptidase N delays onset of experimental cerebral malaria. Parasite Immunol 34:444-7
Lim, Hoyong; Kim, Young Uk; Drouin, Scott M et al. (2012) Negative regulation of pulmonary Th17 responses by C3a anaphylatoxin during allergic inflammation in mice. PLoS One 7:e52666
Wang, Dachun; Morales, John E; Calame, Daniel G et al. (2010) Transplantation of human embryonic stem cell-derived alveolar epithelial type II cells abrogates acute lung injury in mice. Mol Ther 18:625-34
Mueller-Ortiz, Stacey L; Wang, Dachun; Morales, John E et al. (2009) Targeted disruption of the gene encoding the murine small subunit of carboxypeptidase N (CPN1) causes susceptibility to C5a anaphylatoxin-mediated shock. J Immunol 182:6533-9

Showing the most recent 10 out of 20 publications