Mediators Inflamm. 2012;2012:628754.

Inflammatory marker sTREM-1 reflects the clinical stage and respiratory tract obstruction in allergic asthma bronchiale patients and correlates with number of neutrophils.

Bucova M, Suchankova M, Dzurilla M, Vrlik M, Novosadova H, Tedlova E, Urban S, Hornakova E, Seligova M, Durmanova V, Penz P, Javor J, Paulovicova E.

Institute of Immunology, Comenius University, Bratislava, Slovakia. maria.bucova@gmail.com

 

Abstract

The knowledge that asthma is an inflammatory disorder has prompted us to investigate the plasma levels of a new inflammatory marker sTREM-1 that is released from the surfaces of activated neutrophils and monocytes. The plasma levels of sTREM-1 were analysed by a sandwich ELISA test in the cohort of 76 patients with allergic asthma bronchiale and 39 healthy controls. Our results revealed more than 3.5 times higher levels of sTREM-1 in AB patients (92.3 pg/mL ± 125.6) compared with healthy subjects (25.7 pg/mL ± 9.2; P = 0.0001). Higher levels of sTREM-1 were found also in patients with exacerbated AB (170.5 pg/mL ± 78.2) compared with nonexacerbated AB patients (59.1 ± 78.2; P < 0.0001), patients with respiratory tract obstruction (176.4 pg/mL ± 177.8), than those without obstruction (51.99 pg/mL ± 64.0; P < 0.0001) and patients with anti-IgE therapy (P < 0.0001). Levels of sTREM-1 correlated with number of leucocytes (P = 0.002), and absolute number of neutrophils (P = 0.001). Elevated plasma levels of sTREM-1 reflect the severity, state of exacerbation, presence of respiratory tract obstruction in AB patients and together with increased number of neutrophils point to the role of neutrophils in inflammation accompanying AB.

PMID: 22829716

 

Supplements:

TREM-1 (Triggering receptor expressed on myeloid cells), first described in 2000, belongs to a family related to the natural killer cell receptors and is constitutively expressed on the surface of myeloid cells – neutrophils, monocytes, and macrophages (1). Expression of TREM-1 is upregulated after stimulation with bacterial and fungal products, and also sterile noninfectious stimuli.— inflammatory cytokines or other mediators of inflammation, for example, prostaglandin E2 (PGE2) and some endogenous substances released during inflammation — damage-associated molecular patterns (2). The membrane form of TREM-1 can be cleaved from the surface of activated myelocytes by plasma metalloproteinases and its ectodomain is released into microenvironment (3). This soluble molecule (sTREM-1) can be measured in biological fluids and may be useful as a diagnostic tool. The highest levels of sTREM-1 molecules have been found in patients with sepsis (4) and other inflammatory diseases caused mainly by extracellular microorganisms — bacteria and fungi, as well as inflammatory states of noninfectious origin, for example, rheumatoid arthritis (5).

Knowledge that asthma bronchiale (AB) is inflammatory disorder has prompted us to investigate the plasma levels of sTREM-1 in patients suffering from allergic asthma bronchiale. In our study, we investigated the plasma levels of a new inflammatory marker sTREM-1 in 76 pollen  allergy AB patients and 19 healthy subjects. AB patients were divided into four groups: mild intermitent AB (AB1), mild persistent AB (AB2), moderate persistent AB (AB3) and severe persistent AB (AB4) patients. Our results revealed more than 3.5 times higher levels of sTREM-1 in patients with AB compared with healthy subjects without AB and without history of pollen allergy (P = 0.0001), indicating for the presence of inflammatory process in asthma patients. The elevated levels of plasma sTREM-1 significantly correlated with clinical stage and severity of AB (Table 2, Figure 1). The highest levels of sTREM-1 were found in patients with moderate and severe persistent AB. The association of the clinical stage of AB patients with their age is documented in Table 1. We found also significantly higher levels of sTREM-1 in AB patients in exacerbation (EAB) compared with  non-exacerbating AB (NEAB) patients (P < 0.0001). The group of EAB patients had also significantly higher number of leukocytes (P = 0.014) and neutrophils (P = 0.014) than NEAB group of patients (Table 3). Respiratory tract obstruction was also followed by elevated levels of sTREM-1 (P < 0.0001, Table 2), CRP (P = 0.027), leukocytes (P = 0.013), and absolute number of neutrophils (P = 0.008, Table 4). Investigations of plasma levels of sTREM-1 in all subjects of atopic AB patients disclosed the statistically significant correlation of its levels with the clinical stage of AB,respiratory tract obstruction, levels of CRP, the presence of anti-IgE therapy, number of leukocytes, absolute number of neutrophils, and the level of sTREM-1 calculated per one myelocyte, respectively (Table 5).

Fig 1

 

Figure 1 Plasma levels of sTREM-1 in healthy subjects and asthma bronchiale patients. AB: asthma bronchiale,  AB1: mild intermitent AB, AB2: mild persistent AB, AB3: moderate persistent AB, AB4: severe persistent AB,EAB: exacerbated asthma bronchiale, NEAB: non-exacerbated asthma bronchiale, RTO+: asthma with respiratory tract obstruction, RTO-: asthma without respiratory tract obstruction, Anti – IgE+: asthma with anti – IgE therapy, Anti – IgE-: asthma without anti – IgE therapy.

 

 

Tab 1

 

AB: asthma bronchiale, * significance between  AB2 vs. AB1, AB3 vs. AB1, AB4 vs. AB1, ** significance between age of patients in exacerbated vs. non exacerbated asthma, asthma with vs. without respiratory tract obstruction, patients with vs. without  anti-IgE therapy.

 

 

 

Tab 2

 

AB: asthma bronchiale,  STD: standard deviation, IQR: interquartil range, * significance between  AB2 vs. AB1, AB3 vs. AB1, AB4 vs. AB1, EAB: exacerbated asthma bronchiale, NEAB: non-exacerbated asthma bronchiale, RTO+: asthma with respiratory tract obstruction, RTO: asthma without respiratory tract obstruction, ** significance between exacerbated vs. non-exacerbated asthma, asthma with vs. without respiratory tract obstruction, patients with vs. without  anti-IgE therapy.

 

 

 

Tab 3Leu: leukocytes, Neu: neutrophils, Eo: eosinophils, EAB: exacerbated asthma bronchiale, NEAB: non-exacerbated asthma bronchiale.

 

Tab 4

 

Leu: leukocytes, CRP: C- reactive protein, Neu: neutrophils, Eo: eosinophils, RTO+: asthma bronchiale with respiratory tract obstruction, RTO: asthma bronchiale without respiratory tract obstruction.

 

 

 

Tab 5

 

AB: asthma bronchiale, CRP: C-reactive protein. Taking into account more correlated parameters, statistically significant are values when p<0,005.

 

 

References:

1. D. Barraud and S. Gibot, “Triggering receptor expressed on myeloid cell 1,” Critical Care Clinics, vol. 27, no. 2, pp. 265– 279, 2011.

2. E. Ferat-Osorio, N. Esquivel-Callejas, I. Wong-Baeza et al., “The increased expression of TREM-1 on monocytes is associated with infectious and noninfectious inflammatory processes,” Journal of Surgical Research, vol. 150, no. 1, pp. 110–117, 2008.

3. V. Gómez-Pina, A. Soares-Schanoski, A. Rodríguez-Rojas et al., “Metalloproteinases shed TREM-1 ectodomain from lipopolysaccharide- stimulated human monocytes,” Journal of Immunology, vol. 179, no. 6, pp. 4065–4073, 2007.

4. S. Gibot, A. Cravoisy, M. N. Kolopp-Sarda et al., “Timecourse of sTREM (soluble triggering receptor expressed on myeloid cells)-1, procalcitonin, and C-reactive protein plasma concentrations during sepsis,” Critical Care Medicine, vol. 33, no. 4, pp. 792–796, 2005.

4. T.-H. Kim, S. J. Choi, Y. H. Lee, G. G. Song, and J. D. Ji, “Soluble triggering receptor expressed on myeloid cells-1 as a new therapeutic molecule in rheumatoid arthritis,” Medical Hypotheses, vol. 78, no. 2, pp. 270–272, 2012.

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