Abstract:
:The haptoglobin genotype has been demonstrated to be an independent risk factor for CVD in multiple epidemiological studies. The primary function of haptoglobin is to mitigate the deleterious effects of extracorpuscular hemoglobin. We sought to determine if the protein products of the two haptoglobin alleles differed in their ability to modulate the cytokine profile produced by macrophages in response to hemoglobin. Peripheral blood mononuclear cells were isolated from normal human volunteers and cultured in the presence of complexes formed by the protein products of the two different haptoglobin alleles with hemoglobin. The release of specific cytokines in the conditioned media of these cells was assessed by ELISA. We found that the haptoglobin 1 allele protein product-hemoglobin complex stimulated the secretion of significantly more Il-6 and Il-10 than the haptoglobin 2 allele protein product-hemoglobin complex. We demonstrate that the release of these cytokines is dependent on the liganding of the haptoglobin-hemoglobin complex to the CD163 receptor and the activity of casein kinase II. Haptoglobin genotype modulates the balance of inflammatory (Th1) and anti-inflammatory (Th2) cytokines produced by macrophages exposed to free hemoglobin. This may have implications in understanding inter-individual differences in the inflammatory response to hemorrhage.
journal_name
Atherosclerosisjournal_title
Atherosclerosisauthors
Guetta J,Strauss M,Levy NS,Fahoum L,Levy APdoi
10.1016/j.atherosclerosis.2006.04.032subject
Has Abstractpub_date
2007-03-01 00:00:00pages
48-53issue
1eissn
0021-9150issn
1879-1484pii
S0021-9150(06)00245-0journal_volume
191pub_type
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