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Crit Care Med. 2014 May;42(5):e364-72. doi: 10.1097/CCM.0000000000000231.

C4d deposits on the surface of RBCs in trauma patients and interferes with their function.

Author information

1
1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. 2Department of Biomedical Engineering, Tulane University, New Orleans, LA. 3Institute of Surgical Research, San Antonio, TX.

Abstract

OBJECTIVE:

Complement system is activated in patients with trauma. Although complement activation is presumed to contribute to organ damage and constitutional symptoms, little is known about the involved mechanisms. Because complement components may deposit on RBCs, we asked whether complement deposits on the surface of RBC in trauma and whether such deposition alters RBC function.

DESIGN:

A prospective experimental study.

SETTING:

Research laboratory.

SUBJECTS:

Blood samples collected from 42 trauma patients and 21 healthy donors.

INTERVENTION:

None.

MEASUREMENTS AND MAIN RESULTS:

RBC and sera were collected from trauma patients and control donors. RBCs from trauma patients (n = 40) were found to display significantly higher amounts of C4d on their surface by flow cytometry compared with RBCs from control (n = 17) (p < 0.01). Increased amounts of iC3b were found in trauma sera (n = 27) (vs 12 controls, p < 0.01) by enzyme-linked immunosorbent assay. Incubation of RBC from universal donors (type O, Rh negative) with trauma sera (n = 10) promoted C4d deposition on their surface (vs six controls, p< 0.05). Complement-decorated RBC (n = 6) displayed limited their deformability (vs six controls, p < 0.05) in two-dimensional microchannel arrays. Incubation of RBC with trauma sera (n = 10) promoted the phosphorylation of band 3, a cytoskeletal protein important for the function of the RBC membrane (vs eight controls, p < 0.05), and also accelerated calcium influx (n = 9) and enhanced nitric oxide production (n = 12) (vs four and eight controls respectively, p < 0.05) in flow cytometry.

CONCLUSIONS:

Our study found the presence of extensive complement activation in trauma patients and presents new evidence in support of the hypothesis that complement activation products deposit on the surface of RBC. Such deposition could limit RBC deformability and promote the production of nitric oxide. Our findings suggest that RBC in trauma patients malfunctions, which may explain organ damage and constitutional symptoms that is not accounted for otherwise by previously known pathophysiologic mechanisms.

PMID:
24448198
PMCID:
PMC4099476
DOI:
10.1097/CCM.0000000000000231
[Indexed for MEDLINE]
Free PMC Article
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