Endotoxin receptor CD14 in PiZ alpha-1-antitrypsin deficiency individuals.
BACKGROUND
CD14, a receptor for lipopolysaccharides (LPS), is found in both a membrane-bound form (mCD14) and a soluble form (sCD14). It is suggested that sCD14 is mainly released from blood monocytes by serine protease-mediated shedding. Because alpha1-antitrypsin (AAT), an inhibitor of serine proteases, has been shown to regulate CD14 expression in human monocytes in vitro, we sought to investigate plasma levels of sCD14 and monocyte expression of mCD14 in subjects at age 30 years with normal MM and deficient PiZZ and PiSZ genotypes of AAT.


METHODS
Plasma levels of AAT and sCD14 were measured in 75 PiZZ and 34 PiSZ individuals with normal lung function identified from the Swedish neonatal AAT deficiency screening, and in 95 age matched PiMM controls. The mCD14 expression in monocytes from 9 PiZZ, 6 PiSZ and 11 PiMM subjects was analysed by FACS and Quantitative Real Time Reverse Transcription PCA.


RESULTS
As expected, plasma AAT concentrations were PiMM>PiSZ>PiZZ (p < 0.001). Plasma sCD14 levels were higher in PiZZ than in PiMM subjects (p < 0.01). The expression level of mCD14 was higher (1.89-fold) in monocytes isolated from PiZZ subjects compared to PiMM controls (p = 0.00189).


CONCLUSIONS
This study is the first to show higher levels of plasma sCD14 and monocyte mCD14 expression in young, clinically healthy PiZZ AAT subjects.
Sandström
Caroline S
CS
Department of Clinical Sciences, Chronic and Degenerative Disease Research Unit, University Hospital Malmoe, Lund University, S-20502, Malmo, Sweden. Caroline.Sandstrom@med.lu.se
Novoradovskaya
Natalia
N
Cilio
Corrado M
CM
Piitulainen
Eeva
E
Sveger
Tomas
T
Janciauskiene
Sabina
S
D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood*
D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D011971:Receptors, Immunologic; C048071:endotoxin receptor