Low-grade endotoxemia, gut permeability and platelet activation in community-acquired pneumonia.
Platelet activation seems to be implicated in the cardiovascular events occurring in patients with community-acquired pneumonia (CAP) but the underlying mechanism is still unclear. Aim of the study was to assess the mechanism involved in platelet activation in CAP patients.



Two-hundred-seventy-eight consecutive patients hospitalized for CAP were recruited and followed-up until discharge. Hospitalized patients matched for sex, age and comorbidities but without acute infectious diseases were used as controls.



At hospital admission patients disclosed enhanced plasma levels of sP-selectin, a maker of in-vivo platelet activation, serum sNOX2-dp, a marker of NADPH-oxidase activation, serum Lipopolysaccharide (LPS) and serum zonulin, a marker of gut permeability, compared to controls (p < 0.001). Baseline sP-selectin was independently associated to serum LPS, sNOX2-sp and Pneumonia Severity Index score (p < 0.001). Plasma sP-selectin, serum sNOX2-dp, LPS and zonulin coincidentally decreased at hospital discharge (p < 0.001). An in vitro study showed that LPS, at concentration similar to that found in CAP patients, induced sP-selectin release by agonist-activated platelets, a phenomenon that was counteract by treating cells with gp91ds-tat, a specific inhibitor of NOX2.



CAP patients display enhanced platelet activation, which is related to LPS-mediated NOX2 activation. Enhanced gut permeability seems be implicated in enhancing circulating levels of LPS.
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Roberto
R
Cangemi
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Pasquale
P
Pignatelli
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Roberto
R
Carnevale
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Simona
S
Bartimoccia
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Cristina
C
Nocella
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy.
Marco
M
Falcone
Infectious and Tropical Diseases Unit, Department of Clinical Medicine, Sapienza University of Rome, Italy.
Gloria
G
Taliani
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy. Electronic address: francesco.violi@uniroma1.it.
Francesco
F
Violi
D000328:Adult; D000368:Aged; D017714:Community-Acquired Infections / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D019446:Endotoxemia / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007422:Intestines / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000097:blood*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000097:blood / Q000235:genetics / Q000378:metabolism; D019007:P-Selectin / Q000097:blood; D010539:Permeability; D015539:Platelet Activation; D011014:Pneumonia / Q000097:blood / Q000150:complications / Q000503:physiopathology*
D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019007:P-Selectin; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
Blood platelets; Endotoxins; NADPH oxidase; P-selectin; Pneumonia