Gene expression analysis of TREM1 and GRK2 in polymorphonuclear leukocytes as the surrogate biomarkers of acute bacterial infections.
OBJECTIVE
In the acute stage of infectious diseases such as pneumonia and sepsis, sequelae hypercytokinemia and cytokine storm are often observed simultaneously. During bacterial infections, activated polymorphonuclear leukocytes (PMNs) cause inflammation and organ dysfunction in severely ill patients. Gene expression of the triggering receptor on myeloid cells (TREM)-1 and G-coupled-protein receptor kinase (GRK)-2 in PMNs isolated from patients was analysed to identify genes correlated with the severity of pathophysiological conditions.


METHODS
mRNA levels of TREM1 and GRK2 in the PMNs from 26 patients (13 with pneumonia, 5 with severe sepsis, and 8 with septic shock) were analysed by using quantitative real-time PCR. The synthesised soluble form (s)TREM-1 was incubated with normal PMNs to investigate its biological functions in vitro.


RESULTS
Copies of TREM1 transcript were 0.7- to 2.1-fold higher in patients with pneumonia compared to those of normal subjects; the average fold-change was 1.1-fold. The mRNA levels of patients suffering from severe sepsis and septic shock were 0.34- and 0.33-fold lower compared to those of healthy subjects, respectively. TREM1 mRNA levels in 5 of 26 patients in convalescent stages recovered to normal levels. The mRNA levels of GRK2 in the PMNs of patients were also downregulated. The synthesised sTREM-1 upregulated the mRNA levels of TREM1 in normal PMNs.


CONCLUSIONS
TREM1 mRNA levels were inversely correlated with the severity of pathophysiological conditions in acute bacterial infections. The gene expression levels of TREM1 in PMNs isolated from patients with bacterial infections may be used as a surrogate biomarker for determining the severity.
Department of Microbiology & Immunology, Teikyo University School of Medicine. Tokyo 173-8605, Japan.
Tsuneyuki
T
Ubagai
Department of Microbiology & Immunology, Teikyo University School of Medicine. Tokyo 173-8605, Japan.
Ryuichi
R
Nakano
Department of Microbiology & Immunology, Teikyo University School of Medicine. Tokyo 173-8605, Japan.
Hirotoshi
H
Kikuchi
Department of Microbiology & Immunology, Teikyo University School of Medicine. Tokyo 173-8605, Japan.
Yasuo
Y
Ono
D000368:Aged; D001424:Bacterial Infections / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D011014:Pneumonia / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D018805:Sepsis / Q000378:metabolism* / Q000503:physiopathology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D015415:Biomarkers; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; C496567:GRK2 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2
GRK2; Pneumonia; Polymorphonuclear leukocytes; Sepsis; TREM1; real-time PCR