Innate Immune Molecule Surfactant Protein D Attenuates Sepsis-induced Acute Pancreatic Injury through Modulating Apoptosis and NF-κB-mediated Inflammation

Abstract

Sepsis causes multiple-organ dysfunction including pancreatic injury, thus resulting in high mortality. Innate immune molecule surfactant protein D (SP-D) plays a critical role in host defense and regulating inflammation of infectious diseases. In this study we investigated SP-D functions in the acute pancreatic injury (API) with C57BL/6 Wild-type (WT) and SP-D knockout (KO) mice in cecal ligation and puncture (CLP) model. Our results confirm SP-D expression in pancreatic islets and intercalated ducts and are the first to explore the role of pancreatic SP-D in sepsis. CLP decreased pancreatic SP-D levels and caused severe pancreatic injury with higher serum amylase 24 h after CLP. Apoptosis and neutrophil infiltration were increased in the pancreas of septic KO mice (p < 0.05, vs septic WT mice), with lower Bcl-2 and higher caspase-3 levels in septic KO mice (p < 0.05). Molecular analysis revealed increased NF-κB-p65 and phosphorylated IκB-α levels along with higher serum levels of TNF-α and IL-6 in septic KO mice compared to septic WT mice (p < 0.01). Furthermore, in vitro islet cultures stimulated with LPS produced higher TNF-α and IL-6 (p < 0.05) from KO mice compared to WT mice. Collectively, these results demonstrate SP-D plays protective roles by inhibiting apoptosis and modulating NF-κB-mediated inflammation in CLP-induced API.

Surfactant protein D attenuates nitric oxide-stimulated apoptosis in rat chondrocyte by suppressing p38 MAPK signaling

“…SP-D can inhibit TLR4 expression and inflammatory cytokines in human corneal epithelial cells through TLR4 signaling pathway during fungal infection [23]. SP-D can inhibit cell apoptosis and modulating NF-κB-mediated inflammation in sepsis-stimulated acute pancreatic injury [11]. The present study is the first to suggest that SP-D expression was observed in chondrocyte, and explain the critical role in modulation of SP-D in OA progression.…”

“…The structure of SP-D is comprised of four domains, including N-terminus cysteine-rich domain, triple-helical collagen-like domain, neck region and carbohydrate recognition domain (CRD) [6]. Extrapulmonary tissues/organs SP-D expression has been recognized, such as kidney [7], digestive tract and mesentery [8], nasal epithelium [9], salivary glands and saliva [10], pancreas [11], and prostate and reproductive system [12]. Furthermore, SP-D is expressed in the synovial fluid to vary degrees in rheumatoid arthritis (RA), which reveals a characteristic aspect in the pathogenesis of RA as in lung [13,14].…”

Structure, genetics and function of the pulmonary associated surfactant proteins A and D: The extra-pulmonary role of these C type lectins

“…Liu et. al using a mouse model of acute pancreatic injury demonstrated that wild type mice had decreased apoptosis and neutrophil infiltration when compared to SP-D knockout mice, demonstrating the protective effect of SP-D (Liu et al, 2015). Saka et al established the protective effect of SP-D in the devastating neonatal intestinal disease, necrotizing enterocolitis (NEC), by establishing that SP-D could attenuate TLR-4 over-expression in immature embryonal intestine cells (Saka et al, 2016).…”

“…To date, a host of collectins have been described including MBL, SP-A, SP-D, collectin liver 1 (CL-L1), collectin kidney 1 (CL-K1) and conglutinins (Mayer et al, 2017). These collectins recognize and neutralize pathogens by several different mechanisms including aggregation (Tenner et al, 1989), apoptosis (Liu et al, 2015), opsonization (Ferguson et al, 1999; Ghildyal et al, 1999; Hartshorn et al, 1996; Hickling et al, 1999; McIntosh et al, 1996; McNeely and Coonrod, 1994), activation of phagocytosis (Beharka et al, 2002; Ferguson et al, 1999; Nepomuceno et al, 1997; Tenner et al, 1989), inhibition of microbial growth, or modulation of the inflammatory response (Herbein and Wright, 2001; Liu et al, 2015; Saka et al, 2016; Salminen et al, 2008; Sato et al, 2003). Collectins may compete with factors such as LPS for binding to cell surface receptors (Chuang et al, 2011; Ohya et al, 2006; Saka et al, 2016; Vayrynen et al, 2002; Yamada et al, 2004).…”

Differential levels of surfactant protein A, surfactant protein D, and progesterone to estradiol ratio in maternal serum before and after the onset of severe early‐onset preeclampsia

“…4 It has been suggested that both the clinical phenotypes are the result of different degree of placental malperfusion and may have different aetiologies. [8][9][10] Collectins, a type of soluble pattern recognition proteins of in- [11][12][13][14] They compete with the inflammatory agents such as LPS for binding to the cell surface receptors and thus feature centrally in the modulation of inflammatory response. Impaired placental development leads to persistent hypoxia at the feto-maternal interface, enhanced release of apoptotic debris in the maternal circulation, and elevation of systemic inflammatory response.…”