Club cell protein 16 in sera from trauma patients modulates neutrophil migration and functionality via CXCR1 and CXCR2

Abstract

BackgroundClub Cell protein (CC)16 correlates with lung injury and respiratory complications, which are in part triggered by polymorphonuclear leukocytes (PMNL) in severely traumatized patients (TP). CC16 exerts anti-inflammatory and immunosuppressive effects, however, its influence on PMNL functions after trauma is unknown. Here, we evaluated whether CC16 present in sera from TP could modify the biological functions of PMNL.MethodsSera from 16 severely injured TP without pneumonia (no P, n = 8) or with pneumonia (P, n = 8) were collected at admission to emergency department (ED) and 1 day prior pneumonia and pre-incubated with or without anti-CC16 antibody for CC16 neutralization. Samples from the equal post-injury days in the corresponding no P group were used. Neutrophils were isolated from healthy volunteers (HV, n = 5) and incubated with 20% of the serum medium from TP, respectively. In PMNL, CD62L, CD11b/CD18 and CD31 expression, migratory capacity, phagocytosis rate, oxidative burst and apoptosis were investigated. In isolated PMNL, CXCR1 and CXCR2 were neutralized before stimulation with CC16, and oxidative burst, phagocytosis and apoptosis were analyzed in neutrophils and their subsets.ResultsSerum from the P group enhanced significantly PMNL migration compared to no P group, while CC16-neutralization further increased the migratory rate of PMNL in both groups. CC16-neutralization increased significantly the expression of CD62L in the P group at ED. Oxidative burst was significantly increased in the P group vs. no P during the study period. CC16 seemed to have no influence on oxidative burst and phagocytosis in TP. However, in a more controlled study design, CC16 induced a significant increase of oxidative burst and a decrease of apoptosis of CD16+ granulocytes. These effects were markedly observed in mature CD16brightCD62Lbright and immune suppressive CD16brightCD62Ldim neutrophils. In mature subset, CXCR1 and CXCR2 neutralization diminished CC16-induced effects.ConclusionsCC16 in sera from multiply traumatized patients, notably of those with pneumonia, has significant effects on PMNL. The results suggest an association of CC16 with CXCR1 and CXCR2. Our data suggest that CC16 reduces the migratory capacity of PMNL and thus modulates their function in patients with respiratory complications after trauma.

Club Cell Protein 16 Attenuates CD16brightCD62dim Immunosuppressive Neutrophils in Damaged Tissue upon Posttraumatic Sepsis-Induced Lung Injury

“…Since IFN- γ is delayed in its systemic increase compared to other proinflammatory cytokines after trauma [ 57 ], CC16 might also provide late immunosuppressive effects by suppressing IFN- γ , while the immediate effects on PMNL-differentiation may be rather proinflammatory. Increased rates of immature PMNL following CC16 neutralization in the lungs, BALF, and blood might be associated with reducing effects of CC16 on PMNL migration [ 58 ]. On the other hand, it suggests the effect of CC16 to be influenced by the local immune state, as PMNL differentiation differs in unaffected tissue.…”

Secretoglobins in the big picture of immunoregulation in airway diseases

“…76 The anti-inflammatory effect of SCGB1A1 on neutrophils is not limited to IL-8, but also modulates neutrophil migration via other chemokines and their receptors (CXCR1 and CXCR2). 79 In addition, SCGB1A1 mediates the regulation of the innate immune system via dendritic cells, by inhibiting their ability to mobilize T helper 17 (Th17) cells in an OVA-induced allergic rhinitis model. 80 Furthermore, mice lacking SCGB1A1 have strongly reduced cytokine and chemokine responses in the alveolar milieu.…”

Effect of ORF7 of SARS-CoV-2 on the Chemotaxis of Monocytes and Neutrophils In Vitro

“…Neutrophils were isolated from blood samples of healthy human donors using PolymorphPrep (Alere Technologies AS, Oslo, Norway) as previously described [ 21 , 22 ]. Briefly, 5 mL of blood was layered onto 5 mL of PolymorphPrep and centrifuged for 35 min (500 g) at room temperature.…”