Lung Surfactant Accelerates Skin Wound Healing: A Translational Study with a Randomized Clinical Phase I Study

Abstract

Lung surfactants are used for reducing alveolar surface tension in preterm infants to ease breathing. Phospholipid films with surfactant proteins regulate the activity of alveolar macrophages and reduce inflammation. Aberrant skin wound healing is characterized by persistent inflammation. The aim of the study was to investigate if lung surfactant can promote wound healing. Preclinical wound models, e.g. cell scratch assays and full-thickness excisional wounds in mice, and a randomized, phase I clinical trial in healthy human volunteers using a suction blister model were used to study the effect of the commercially available bovine lung surfactant on skin wound repair. Lung surfactant increased migration of keratinocytes in a concentration-dependent manner with no effect on fibroblasts. Significantly reduced expression levels were found for pro-inflammatory and pro-fibrotic genes in murine wounds. Because of these beneficial effects in preclinical experiments, a clinical phase I study was initiated to monitor safety and tolerability of surfactant when applied topically onto human wounds and normal skin. No adverse effects were observed. Subepidermal wounds healed significantly faster with surfactant compared to control. our study provides lung surfactant as a strong candidate for innovative treatment of chronic skin wounds and as additive for treatment of burn wounds to reduce inflammation and prevent excessive scarring.

Whole genome characterization of autochthonous Bos taurus brachyceros and introduced Bos indicus indicus cattle breeds in Cameroon regarding their adaptive phenotypic traits and pathogen resistance

“…In Namchi, although such GO terms were not significantly enriched, genes such as ADAMTSL1, an ADAMTS like gene, OR9G1, an olfactory receptor (OR) and the surfactant protein SFTPD were identified carrying either missense variants or frameshift variants (Additional file 3 Table S3). These genes are often reported in the context of heat stress via their interaction with heat shock proteins, but have been also often reported in the context of wound healing [29,30]. This would imply some genes that contribute to important resistance traits are passed onto hybrid offspring in the Namchi, and might therefore be interesting candidates for further research on increasing trypanotolerance in WAS.…”

“…However, several missense variants of high impact were found on an Interferon-inducible GTPase gene (Additional file 3 Table S7). These GTPases provide host resistance to a variety of viral, bacterial and protozoan pathogens through the sequestration of microbial proteins, manipulation of vesicle trafficking, regulation of antimicrobial autophagy [29,30], which are all congruent for a significant role in the adaptation to infectious diseases.…”

Whole genome characterization of autochthonous Bos taurus brachyceros and introduced Bos indicus indicus cattle breeds in Cameroon regarding their adaptive phenotypic traits and pathogen resistance

“…In Namchi, although such GO terms were not signi cantly enriched, genes such as ADAMTSL1, an ADAMTS like gene, OR9G1, an olfactory receptor (OR) and the surfactant protein SFTPD were identi ed carrying either missense variants or frameshift variants (Additional le 3 Table S3). These genes are often reported in the context of heat stress via their interaction with heat shock proteins, but have been also often reported in the context of wound healing [38][39]. This would imply some genes that contribute to important resistance traits are passed onto hybrid offspring in the Namchi, and might therefore be interesting candidates for further research on increasing trypanotolerance in WAS.…”

“…However, several missense variants of high impact were found on an Interferon-inducible GTPase gene (Additional le 3 Table S7). These GTPases provide host resistance to a variety of viral, bacterial and protozoan pathogens through the sequestration of microbial proteins, manipulation of vesicle tra cking, regulation of antimicrobial autophagy [38,39], which are all congruent for a signi cant role in the adaptation to infectious diseases.…”

“…They are essential for avoiding danger, food search, reproduction, and behaviour [34]. Ors have been linked to heat stress but were also reported to accelerate wound healing [35][36][37][38], where chemokines play a critical role by enabling the phagocytic leukocytes of the immune system to be the rst line of defense against infectious agents, such as protozoa and helminth parasites [39]. The tolerance of Namchi cattle against trypanosomiasis (trypanotolerance) caused by the protozoan parasites Trypanosoma congolense, T. vivax and T. brucei is actively driven by the innate immune response.…”