Macrophage-Derived Chemokine (CCL22) Is a Novel Mediator of Lung Inflammation Following Hemorrhage and Resuscitation

Abstract

Resuscitation of patients after hemorrhage often results in pulmonary inflammation and places them at risk for the development of acute respiratory distress syndrome. Our previous data indicate that macrophage-derived chemokine (MDC/CCL22) is elevated after resuscitation, but its direct role in this inflammatory response is unknown. MDC signaling through the C-C chemokine receptor type 4 (CCR4) is implicated in other pulmonary proinflammatory conditions, leading us to hypothesize that MDC may also play a role in the pathogenesis of lung inflammation following hemorrhage and resuscitation. To test this, C57BL/6 mice underwent pressure-controlled hemorrhage followed by resuscitation with lactated Ringer’s solution. Pulmonary inflammation and inflammatory cell recruitment were analyzed with histological staining, and serum- and tissue-level cytokines were measured by ELISA. Pulmonary inflammation and cell recruitment following hemorrhage and resuscitation were associated with systemic MDC levels. Inhibition of MDC via injection of a specific neutralizing antibody prior to hemorrhage and resuscitation significantly reduced pulmonary levels of the chemotactic cytokines KC, MIP-2, and MIP-1α as well as inflammatory cell recruitment to the lungs. Intravenous administration of recombinant MDC prior to resuscitation augmented pulmonary inflammation and cell recruitment. Histological evaluation revealed the expression of CCR4 within the bronchial epithelium, and in vitro treatment of activated bronchial epithelial cells with MDC resulted in production and secretion of neutrophil chemokines. The present study identifies MDC as a novel mediator of lung inflammation after hemorrhage and resuscitation. MDC neutralization may provide a therapeutic strategy to mitigate this inflammatory response.

Quantitative profiling of cytokines and chemokines in DOCK8‐deficient and atopic dermatitis patients

“…It was downregulated in DOCK8 patients when compared to Ctrls (Figure D). MDC was shown to be involved in various immune responses and elimination of pathogens, allergic reactions, and inflammation in the lungs . Hence, upregulation of MDC (Figure E) is consistent with the clinical features (infections, allergies, and pneumonia) seen in the DOCK8‐deficient patients.…”

Distinct Dynamics of Stem and Progenitor Cells in Blood of Polytraumatized Patients

“…In agreement with our initial correlative analyses, we found in LoLiNuts pro-inflammatory cytokines like IL-6, IL-8, and G-SCF and the damage parameter CK to be increased at the early stages of trauma (at 0–3 h IL-6, IL-8, and G-CSF, at 24 h IL-8 and at 48 h CK), implying that high levels of these cytokines at early time points after trauma are linked to a low ANSP score in the 48 h to 120 h interval. Macrophage-derived chemokine (MDC), which is a ligand for CCR4 and has been already implemented as a mediator of lung inflammation upon trauma (27) while being on average elevated at the 120 h time-point (Fig. 3), was the only factor of all the mediators analyzed that presented with a higher concentration at the 120 h time-point in HiLiNuts.…”

High Abundance of genus Prevotella in the gut of perinatally HIV-infected children is associated with IP-10 levels despite therapy

“…In contrast to the previous study in adults 25 , 27 , we found that relative abundance of Prevotella was indirectly associated with peripheral CD4 count and directly associated with MDC in perinatally HIV-infected children. MDC has emerged as novel modulator of lung inflammation in mice 48 and an inflammatory marker to assess the severity of atopic dermatitis in children and infants 49 . More recently, the increased levels of MDC in HIV-infected adults have also been reported 50 .…”