Chemokine receptor expression in peripheral blood monocytes from patients with neovascular age-related macular degeneration.
OBJECTIVE
Chemokine signaling and monocytes/macrophages were implicated in the pathogenesis of AMD. We tested the association between chemokines involved in monocyte recruitment and AMD.


METHODS
Immunophenotyping for white blood cell (WBC) populations including CD14++CD16- and CD14+CD16+ monocytes, CD19+, CD3+, and CD16+ lymphocytes, and chemokine receptors CCR1, CCR2, CCR5, CX(3)CR1, and CXCR4 was performed on peripheral blood from treatment-naïve neovascular AMD (NV-AMD) patients and controls. The mRNA level of chemokine receptors in monocytes was measured with quantitative-PCR. Systemic levels of major chemokine ligands CCL2, CCL5, CCL3, and CXCL10 were evaluated by ELISA. Genotyping was performed for risk SNPs for AMD in the CFH, C3, and HTRA1 genes.


RESULTS
The percentage of WBC subpopulations tested was similar between NV-AMD patients (n = 18) and controls (n = 20). CD14+CD16+ monocyte subpopulation showed a 3.5-fold increased expression of CCR1 (P = 0.039; t-test) and a 2.2-fold increased expression of CCR2 (P = 0.027) in patients compared with controls. Increased CCR1 and CCR2 expression was correlated with each other in patients (R(2) = 0.64, P < 0.0001), but not controls (R(2) = 0.02, P = 0.57). Increased mRNA levels of CCR1 (1.6-fold, P = 0.037) and CCR2 (1.6-fold, P = 0.007) were found in monocytes from NV-AMD patients. Chemokine receptor expression was not correlated with the presence of risk SNPs, and was not associated with blood chemokine levels.


CONCLUSIONS
CCR1 and CCR2 are coupregulated on the CD14+CD16+ monocyte population in NV-AMD patients. These data implicate CD14+CD16+ monocytes and chemokine signaling in AMD. Additional investigation is needed to elucidate the role of these monocytes and their potential as a biomarker or therapeutic target for AMD.
Department of Ophthalmology, Hadassah–Hebrew University Medical Center, Jerusalem, Israel.
Michelle
M
Grunin
Tal
T
Burstyn-Cohen
Shira
S
Hagbi-Levi
Amnon
A
Peled
Itay
I
Chowers
D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; D016207:Cytokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine