Impact of C-reactive protein (CRP) on surfactant function.
Plasma levels of the acute-phase reactant, C-reactive protein (CRP), increase up to one thousand-fold as a result of trauma or inflammation. CRP binds to phosphorylcholine (PC) in a calcium-ion dependent manner. The structural homology between PC and the major phospholipid component of surfactant, dipalmitoyl phosphatidylcholine (DPPC), led to the present study in which we examined if CRP levels might be increased in patients with adult respiratory distress syndrome (ARDS), and subsequently interfere with surfactant function. Our results showed that CRP levels in the bronchoalveolar fluid (BALF) was increased in patients with ARDS (97.8 +/- 84.2 micrograms/mg total protein vs. 4.04 +/- 2.2 micrograms/mg total protein in normals). Our results show that CRP binds to liposomes containing DPPC and phosphatidylglycerol (PG). As a result of this interaction, CRP inhibits the surface activity of a PG-DPPC mixture when tested with a Wilhelmy surfactometer or with the Enhorning pulsating bubble apparatus. Furthermore, the surface activity of a clinically used surfactant replacement, Surfactant TA (2 mg/ml), was also severely impaired by CRP in a dose-dependent manner (doses used ranging from 24.5 to 1,175 micrograms/ml). In contrast, human serum albumin (HSA) at 500 and 900 micrograms/ml had no inhibitory effect on Surfactant TA surface activity. These results suggest that CRP, although not an initiating insult in ARDS, may contribute to the subsequent abnormalities of surfactant function and thus the pathogenesis of the pulmonary dysfunction seen in ARDS.
Li
J J
JJ
Department of Surgery, Shriners Burns Institute, Boston, MA 02114.
Sanders
R L
RL
McAdam
K P
KP
Hales
C A
CA
Thompson
B T
BT
Gelfand
J A
JA
Burke
J F
JF
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis / Q000378:metabolism*; D002097:C-Reactive Protein / Q000302:isolation & purification / Q000378:metabolism*; D002794:Choline / Q000031:analogs & derivatives*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007457:Iodine Radioisotopes; D008081:Liposomes / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000502:physiology; D012128:Respiratory Distress Syndrome / Q000378:metabolism*; D013500:Surface Tension
D007457:Iodine Radioisotopes; D008081:Liposomes; D011663:Pulmonary Surfactants; D010767:Phosphorylcholine; D015060:1,2-Dipalmitoylphosphatidylcholine; D002097:C-Reactive Protein; D002794:Choline