Serum Amyloid P Contained in Alveolar Fluid From Patients With Acute Respiratory Distress Syndrome Mediates the Inhibition of Monocyte Differentiation into Fibrocyte

Marc Garnier (1) , Arnaud A Mailleux (2, 3, 4) , Valérie Besnard (5, 2, 6, 7, 3) , Paer S Abback (8) , Véronique Leçon , Mathilde Neuville (9) , Aurélie Gouel , Bruno Crestani (10, 11, 12, 13) , Monique Dehoux (10) , Christophe Quesnel (10)

1 CHU Tenon [AP-HP]
2 PHERE (UMR_S_1152 / U1152) - Physiopathologie et Epidémiologie des Maladies Respiratoires
3 USPC - Université Sorbonne Paris Cité
4 DHU FIRE Centre de compétence des maladies pulmonaires rares
5 Université Paris Diderot, Sorbonne Paris Cité, Paris, France
6 Département Hospitalo-Universitaire Fibrosis, Inflammation, Remodeling in cardiovascular, respiratory and renal diseases (Paris)
7 LabEx Inflamex
8 Hôpital Beaujon [AP-HP]
9 Service de réanimation médicale et infectieuse
10 Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire
11 Service de Pneumologie A
12 Département Hospitalo-universtaire FIRE (Fibrosis, Inflammation and Remodeling)
13 Service de pneumologie A

Alveolar 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. Design: Experimental in vitro investigation. Setting: Two ICUs of a teaching hospital. Patients: Twenty-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. Interventions: Peripheral 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 bronchoalveolar 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 Results: Acute respiratory distress syndrome peripheral blood mononuclear cells had a threefold 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 bronchoalveolar 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. Conclusions: The presence of fibrocytes in the lung during acute respiratory distress syndrome could result in a balance between

Mots clés: acute respiratory distress syndrome; fibrocyte; monocyte; peripheral blood mononuclear cell; serum amyloid P

Domaines: Sciences du Vivant [q-bio]

Marc Garnier, Arnaud A Mailleux, Valérie Besnard, Paer S Abback, Véronique Leçon, et al.. Serum Amyloid P Contained in Alveolar Fluid From Patients With Acute Respiratory Distress Syndrome Mediates the Inhibition of Monocyte Differentiation into Fibrocyte. Critical Care Medicine, 2016, 44, pp.e563 - e573. ⟨10.1097/ccm.0000000000001612⟩. ⟨hal-04412487⟩