Journal
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 140, Issue 2, Pages 230-240Publisher
WILEY
DOI: 10.1111/j.1365-2249.2005.02764.x
Keywords
blood-borne pathogens; complement receptor; CR1; immune clearance; transgenic mouse
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Funding
- NIAID NIH HHS [R21 AI057983, R21 AI57983] Funding Source: Medline
- PHS HHS [R01 42987, R0116274] Funding Source: Medline
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Complement receptor 1 (CR1) on the surface of human erythrocytes facilitates intravascular clearance of complement-opsonized pathogens. The need for complement activation can be circumvented by directly coupling the organism to CR1 using a bispecific monoclonal antibody heteropolymer (HP). Lack of a functional homologue to CR1 on mouse erythrocytes has made it difficult to study HP-dependent clearance of pathogens in small animals. We have developed a transgenic mouse that expresses human CR1 on erythrocytes. CR1 antigen is of appropriate size and in a clustered distribution as confirmed by immunoblotting and fluorescence microscopy, respectively. HP that immobilized bacteriophage Phi X174 prototype pathogen to erythrocyte CR1 of the transgenic mice increased the rate of clearance of the virus compared with HP that bound bacteriophage, but not CR1. This transgenic mouse model will allow evaluation of different HPs for their in vivo efficacy and potential as human therapeutics.
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