Complement component C5a activates ICAM-1 expression on human choroidal endothelial cells.
OBJECTIVE
The complement system plays a crucial role in the progression of age-related macular degeneration (AMD). In this study, the authors sought to evaluate the pathophysiologic roles of complement components C3a and C5a in the human choroid in AMD.


METHODS
Human RPE/choroid was assayed for the presence of C3a and C5a receptors (C3aR and C5aR) using RT-PCR and immunohistochemistry. Choroidal endothelial cell migration and proliferation were evaluated in the presence of C5a. Organ cultures of human choroid were incubated in C5a or bovine serum albumin (BSA) followed by quantitative immunohistochemistry and quantitative PCR for ICAM-1. AMD patients and controls were genotyped at SNPs in the C5R1 and C3AR1 genes.


RESULTS
C5aR, but not C3aR, was detected in human choroid. C5a did not promote endothelial cell migration or proliferation. However, choriocapillaris endothelial cells in organ culture responded to C5a by increasing ICAM-1 mRNA and protein. No significant association of SNP genotypes was detected in AMD patients at the C3AR1 and C5R1 genes.


CONCLUSIONS
The generation of C5a peptides may lead to activation of choriocapillaris endothelial cells in AMD. Activation of the choroidal endothelium may affect the progression of AMD by recruitment of monocytes, leading to additional sequelae of AMD pathogenesis.
Skeie
Jessica M
JM
Department of Biomedical Engineering, University of Iowa College of Engineering, Iowa City, Iowa, USA.
Fingert
John H
JH
Russell
Stephen R
SR
Stone
Edwin M
EM
Mullins
Robert F
RF
D002465:Cell Movement; D002829:Choroid / Q000098:blood supply*; D015926:Complement C3a / Q000502:physiology; D015936:Complement C5a / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D008268:Macular Degeneration / Q000378:metabolism; D009924:Organ Culture Techniques; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C488033:C5AR1 protein, human; D012333:RNA, Messenger; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C085567:complement C3a receptor; D018799:Intercellular Adhesion Molecule-1; D015926:Complement C3a; D015936:Complement C5a