The Clinical Significance Of Expression Of The Toll-like Receptor 4 On Cd14~+ Monocytes In Peripheral Blood Of Patients With Chronic Obstructive Pulmonary Disease

Objective: Chronic Obstructive Pulmonary Disease （COPD） is a kind ofchronic inflammatory disease in the airway, respiratory tract infections andenvironmental exposures have an important influence on the developing ofCOPD and the disease progression. As an important component of the innateimmune system, TLRs are the link between environmental exposures andregulation of adaptive immunity. The role of TLRs in pathogenesis of COPDhas been noted recently. TLR4 is one of the important members of the TLRsfamily, which express richly on monocyte-macrophage surface, it recognizeprimarily gram-negative bacteria lipopolysaccharide （LPS） and slsoparticipate in the recognition of endogenic ligand such as heat shock protein,fibrinogen, tissue matrix disintegration products. This experiment studies theexpression of TLR4 on CD14⁺monocytes in peripheral blood of acuteexacerbation stage of COPD patients （AECOPD）, stable chronic obstructivepulmonary disease patients and healthy people, to explore the relationshipbetween inherent immunity deficiency and the pathogenesis of COPD, whichmake a better understanding that the role of TLR4 in the forming of themechanism of airway inflammation in COPD patients, and understand thecorrelation between the expression level of TLR4 and the severity of COPD;to explore the influence of glucocorticoid on the level of TLR4 in theperipheral blood mononuclear cells, then provides new theory for theprevention and control of COPD. Material: To select 30 cases patients who were diagnosed as AECOPDin our internal hospitalization. Based on the disease severity, these patientswere divided into two subgroups: Light-moderate group of 15 cases,severe-slightly severe group of 15 cases, the same basic treatment （foranti-infection, absorbing oxygen, relaxing the bronchial smooth muscle,relieving cough and other symptomatic treatment） was given, addedglucocorticoid to the severe-slightly severe group of AECOPD patients. Aftertwo weeks treatment, the symptoms and signs of AECOPD patients toimprove get into the clinical remission period, which will be regarded as astable COPD group. To select 30 cases who were healthy over the sameperiod as control group. All selected people were collected 2 ml peripheralvenous blood. Flow cytometry were used to analyze relative meanfluorescence intensity （rmfi） and relative positive cell percent （rpcp） of TLR4for CD14 positive peripheral blood monocytes. All AECOPD patients weremeasured by conventional pulmonary function test （FEV₁percentage ofpredicted value, FEV1/FVC value）. Experimental data analysised by theSPSS17.0 statistical analysis software, measurement data expressed by±s,the expression of TLR4 in different state of COPD and correlations wereanalysised by T test and Pearson’s correlation coefficients.Results:1 The expression of TLR4 on CD14⁺monocytes in peripheral blood ofacute exacerbation stage of COPD （AECOPD） group, stable chronicobstructive pulmonary disease group and normal control groupThe rmfi of TLR4 on CD14⁺monocytes in peripheral blood of acuteexacerbation stage of chronic obstructive pulmonary disease （AECOPD）patients was 5.14±0.26, and the rpcp was（4.24±0.17）%, while similar to that of stable chronic obstructive pulmonary disease patients [4.46±0.24 and（3.49±0.24）% respectively, all p>0.05], AECOPD group and COPD groupare both significantly lower than those of the normal control group[13.75±0.28 and（10.25±0.13）% respectively, all p<0.01].2 The expression of TLR4 on CD14+monocytes in peripheral blood ofdifferent serious extent in acute exacerbation stage of COPD （AECOPD）groupThe rmfi of TLR4 on CD14+monocytes in peripheral blood ofsevere-slightly severe AECOPD patients was 3.12±0.15, and the rpcp was（3.17±0.10）%, both significantly lower than the light-moderate group[5.48±0.23 and（5.12±0.20）% respectively, all p<0.01].3 The expression of TLR4 on CD14+monocytes in peripheral blood ofsevere-slightly severe AECOPD patients before glucocorticoid treatment andlater glucocorticoid treatmentThe rmfi of TLR4 on CD14+monocytes in peripheral blood ofsevere-slightly severe AECOPD patients before glucocorticoid treatment was3.12±0.15, and the rpcp was （3.17±0.10）%, both significantly lower than laterglucocorticoid treatment [5.24±0.25 and（5.44±0.19）% respectively, allp<0.01], before glucocorticoid treatment and later glucocorticoid treatmentare both significantly lower than those of the normal control group[13.75±0.28 and（10.25±0.13）% respectively, all p<0.01].4 The correlation between the level of TLR4 on CD14+monocytes inperipheral blood and pulmonary function of acute exacerbation stage ofCOPD patients （AECOPD）The expression of TLR4 on CD14+monocytes in peripheral blood ofacute exacerbation stage of COPD （AECOPD） patients was positively correlated with the lung function parameters, including FEV1percentage ofpredicted value and FEV1/FVC ) （all p<0.001）, r1=0.824, r2=0.756.Conclusions：1. TLR4 participated in airway inflammation response of AECOPD, it isan important link of AECOPD waterfall inflammatory response.2. The rmfi and rpcp of TLR4 on CD14⁺monocytes in peripheral bloodof AECOPD and stable chronic obstructive pulmonary disease patients aredepressed, the results suggested that the innate immunodeficiency played animportant role in the pathogenesis of COPD.3. The expression of TLR4 on CD14⁺monocytes in peripheral blood ofacute exacerbation stage of COPD （AECOPD） patients was positivelycorrelated with the lung function parameters, including FEV1percentage ofpredicted value and FEV1/FVC), the results suggested that the downregulation of TLR4 was associated with the disease progression, and theexpression of TLR4 is an important indicator to disease severity.4. Glucocorticoid can promote the expression of TLR4 on CD14⁺monocytes in peripheral blood of severe-slightly severe AECOPD patients,the results suggested that glucocorticoid through inhibit airway inflammationresponse and enhance the defensive function of innate immune system to treatCOPD.