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Function is Dissociated From Activation-Related Immunophenotype on Phagocytes From Patients With SIRS/Sepsis Syndrome

Flores-Mejía, Luis A.*,†; Cabrera-Rivera, Graciela L.*,‡; Ferat-Osorio, Eduardo*,§; Mancilla-Herrera, Ismael||; Torres-Rosas, Rafael; Boscó-Garate, Ilka B.*; López-Macías, Constantino*; Isibasi, Armando*; Cérbulo-Vazquez, Arturo#; Arriaga-Pizano, Lourdes A.*

doi: 10.1097/SHK.0000000000001314
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ABSTRACT Sepsis is a life-threatening condition associated with failure of at least one organ in the presence of infection. Along with SIRS, the acute systemic inflammatory syndrome without documented infection, sepsis represents a main health problem in intensive care units around the world. Hypercytokinemia and overexpression of activation-markers on leukocytes are frequently reported in SIRS/sepsis. Leukocyte functions including antibody mediated-phagocytosis, pathogen recognition, and migration appear to be disabled in SIRS/septic patients. Our aim was to evaluate the so-called activation immunophenotype and functions related to infection contention in phagocytes from patients with sepsis. We analyzed blood samples from 44 patients with SIRS/sepsis and 14 healthy volunteers. CD16, CD69, CD64, CCR7, and TREM-1 levels were determined on the surface of neutrophils and monocytes. Phagosome maturation and p38, STAT3, and STAT5 phosphorylation were evaluated in these phagocytes. As expected, sepsis and SIRS patients had increased serological levels of pro- and anti-inflammatory cytokines. E coli internalization was not increased in monocytes from patients with SIRS/sepsis, despite increased numbers of circulating neutrophils and monocytes (P < 0.05) and overexpression of CD64 and CD69 in neutrophils (P < 0.05), TREM-1 (P < 0.01), CD69 (P < 0.001), and CCR7 (P < 0.05). Moreover, phagosome maturation was decreased in phagocytes from patients with SIRS/sepsis syndrome (P < 0.00001). Furthermore, p38 and STAT-3 phosphorylation elicited by LPS or IL-10 (respectively) was diminished in neutrophils and monocytes from patients (P < 0.05). Our results indicate that “activation markers” may not reflect higher functionality, so a more profound analysis should be made before assuming that the activated immunophenotype means increased phagocyte responses.

*Unidad de Investigación Médica en Inmunoquímica, Centro Médico Nacional “Siglo XXI,” Instituto Mexicano del Seguro Social, Mexico City, Mexico

Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico

Posgrado en Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico

§Servicio de Gastrocirugía, UMAE Hospital de Especialidades, Centro Medico Nacional “Siglo XXI,” Instituto Mexicano del Seguro Social, Mexico City, Mexico

||Departamento de infectología e inmunología, Instituto National de Perinatología (INPer), Lomas Virreyes Mexico City, Mexico

Laboratorio de Inmunología, Facultad de Odontología, Universidad Autónoma “Benito Juárez” de Oaxaca, Oaxaca, Mexico

#Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico

Address reprint requests to Lourdes A. Arriaga-Pizano, MD, PhD, Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Avenida Cuauhtémoc 330, Colonia Doctores, CP 06720, Ciudad de México, Mexico. E-mail: landapi@hotmail.com

Received 19 October, 2018

Revised 9 November, 2018

Accepted 19 December, 2018

This work was funded by CONACYT (project number SALUD-2013-01-202621) and IMSS (project number FIS/IMSS/PROT/G15/1484) assigned to LAA-P. LAF-M is a doctoral student from Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM) and received a CONACYT fellowship (257960) and IMSS complementary support (99096705).

LAF-M, C-RL, and IM-H contributed to the design of the study and to the acquisition and analysis of the data. EF-O and AC-V contributed to the design of the study, selection, enrollment, monitoring of patients, and the revision of the manuscript. IBB-G contributed to the selection, enrollment, and monitoring of patients. RT-R contributed to the analysis of data and revision of the manuscript. CL-M and AI contributed to the design of the study and revision of the manuscript. L-MLA, and LAA-P wrote the manuscript.

The authors report no conflicts of interest.

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