• Marc Garnier, Arnaud A Mailleux, Valérie Besnard, Paer S Abback, Véronique Leçon, Mathilde Neuville, Aurélie Gouel, Bruno Crestani, Monique Dehoux, and Christophe Quesnel.
• 1Unité INSERM 1152, Université Paris Diderot Sorbonne Paris Cité, Paris, France. 2APHP Hôpital Tenon, Département d'Anesthésie et Réanimation, Paris, France. 3Université Pierre et Marie Curie Sorbonne Université, Paris, France. 4APHP Hôpital Beaujon, Département d'Anesthésie et Réanimation, Paris, France. 5APHP Hôpital Bichat, Service de Biochimie, Paris, France. 6APHP Hôpital Bichat, Service de Réanimation médicale, Paris, France. 7APHP Hôpital Bichat, Département d'Anesthésie et Réanimation, Paris, France. 8APHP Hôpital Bichat, Service de Pneumologie, DHU FIRE, Paris, France.
• Crit. Care Med. 2016 Jul 1; 44 (7): e563-73.

ObjectiveAlveolar fibrocytes are monocyte-derived mesenchymal cells associated with poor prognosis in patients with acute respiratory distress syndrome. Our aims were to determine the following: 1) the ability of monocytes from acute respiratory distress syndrome patients to differentiate into fibrocytes; 2) the influence of the acute respiratory distress syndrome alveolar environment on fibrocyte differentiation; and 3) mediators involved in this modulation, focusing on serum amyloid P.DesignExperimental in vitro investigation.SettingTwo ICUs of a teaching hospital.PatientsTwenty-five patients (19 mild-to-severe acute respiratory distress syndrome and six matched ventilated controls without acute respiratory distress syndrome) were enrolled. Six healthy volunteers served as non-ventilated controls.InterventionsPeripheral blood mononuclear cells were isolated from acute respiratory distress syndrome, ventilated controls, and non-ventilated controls blood and cultured in vitro. Fibrocytes were counted at basal condition and after culture with broncho-alveolar lavage fluid. Plasma and broncho-alveolar lavage fluid serum amyloid P contents were determined by western blot and enzyme-linked immunosorbent assay. Serum amyloid P was located in normal and acute respiratory distress syndrome lung by immunohistochemistry.Measurements And Main ResultsAcute respiratory distress syndrome peripheral blood mononuclear cells had a three-fold increased ability to differentiate into fibrocytes compared to ventilated controls or non-ventilated controls. Acute respiratory distress syndrome broncho-alveolar lavage fluid inhibited by 71% (55-94) fibrocyte differentiation compared to saline control. Ventilated controls' broncho-alveolar lavage fluid was a less potent inhibitor (51% [23-66%] of inhibition), whereas non-ventilated controls' broncho-alveolar lavage fluid had no effect on fibrocyte differentiation. Serum amyloid P concentration was decreased in plasma and dramatically increased in broncho-alveolar lavage fluid during acute respiratory distress syndrome. Alveolar serum amyloid P originated, in part, from the release of serum amyloid P associated with lung connective tissue during acute respiratory distress syndrome. Serum amyloid P depletion decreased the inhibitory effect of acute respiratory distress syndrome broncho-alveolar lavage fluid by 60%, whereas serum amyloid P replenishment of serum amyloid P-depleted acute respiratory distress syndrome broncho-alveolar lavage fluid restored their full inhibitory effect.ConclusionsThe presence of fibrocytes in the lung during acute respiratory distress syndrome could result in a balance between higher ability of monocytes to differentiate into fibrocytes and the inhibitory effect of the alveolar environment, mainly dependent on serum amyloid P.

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