ABSTRACT
INTRODUCTION: Numerous clinical studies related the plasma level of C-reactive protein (CRP) to the erythrocyte sedimentation rate (ESR) independent of the kind of disease. The molecular regulation of the process is unknown. METHODS: We performed a meta-analysis of 10 previous studies and experimentally probed for a direct action of CRP on red blood cells (RBCs) by different methods including determination of a microscopic aggregation index, Ca(2+) imaging and analysis of sedimentation experiments. RESULTS: The meta-analysis revealed a statistically significant correlation (Pearson coefficient of 0.37; P < 0.0001), but we could not find any experimental evidence for a direct CRP-RBC interaction. Instead, we could confirm a correlation between fibrinogen level and ESR. CONCLUSION: Therefore, we concluded that CRP and ESR cannot account for nor replace each other as a diagnostic measure. The correlation between CRP level and ESR is most probably caused by fibrinogen, because its increase coincides with elevated CRP levels.
Subject(s)
Arthritis, Rheumatoid/blood , C-Reactive Protein/metabolism , Colitis, Ulcerative/blood , Endocarditis/blood , Erythrocyte Aggregation , Osteomyelitis/blood , Pancreatitis/blood , Arthritis, Rheumatoid/diagnosis , Blood Sedimentation , Calcium/blood , Colitis, Ulcerative/diagnosis , Endocarditis/diagnosis , Erythrocytes/metabolism , Erythrocytes/pathology , Fibrinogen/metabolism , Humans , Molecular Imaging , Osteomyelitis/diagnosis , Pancreatitis/diagnosis , Regression Analysis , Severity of Illness IndexABSTRACT
The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule network and in arterioles at low shear rates or stasis. Thanks to an excellent agreement between combined experimental and numerical approaches, we show that despite the large shear rates present in microcapillaries, the presence of either fibrinogen or the synthetic polymer dextran leads to an enhanced formation of robust clusters of red blood cells, even at haematocrits as low as 1%. Robust aggregates are shown to exist in microcapillaries even for fibrinogen concentrations within the healthy physiological range. These persistent aggregates should strongly affect cell distribution and blood perfusion in the microvasculature, with putative implications for blood disorders even within apparently asymptomatic subjects.
