RP S19 C-terminal peptide trimer acts as a C5a receptor antagonist

AbstractWe have demonstrated that ribosomal protein S19 (RP S19) polymer, when crosslinked between Lys122 and Gln137 by activated coagulation factor XIII, acts as a C5a receptor (C5aR) antagonist/agonist. Based on experimental data obtained using RP S19 analog peptide and recombinant protein monomer, we suggested that L131DR, I134AGQVAAAN and K143KH moieties in the RP S19 C‐terminus act in, respectively, C5aR binding, penetration of the plasma membrane, and interaction with either an apoptosis-inducing molecule in neutrophils (delta lactoferrin) or a calcium channel-activating molecule (annexin A3) to induce the p38 MAPK pathway in macrophages. Recently, we observed RP S19 trimer in serum. To study the effects of this RP S19 trimer on C5aR, we prepared mutant RP S19 C‐terminal peptide (RP S19122-145) dimer and trimer, and examined their chemotactic activities and signal transduction pathways in human C5aR-overexpressing squamous cell carcinoma HSC-1 (HSC-1C5aR) cells using 24 trans-well chamber and western blotting assays, respectively. HSC-1C5aR cells were attracted by RP S19122-145 dimer and vice versa by RP S19122-145 trimer. The RP S19122-145 dimer-induced attraction was competitively blocked by pre-treatment with RP S19122-145 trimer. Moreover, RP S19122-145 trimer-induced p38 MAPK phosphorylation was stronger than RP S19122-145 dimer-induced p38 MAPK phosphorylation. RP S19122-145 trimer appeared to act as a C5aR antagonist. The agonistic and antagonistic effects of RP S19122-145 dimers and trimers were reflected by monocytic, THP-1-derived macrophage-like cells. Unlike the C5aR agonist C5a, which acts at the inflammation phase of acute inflammation, RP S19 trimer might act as a C5aR antagonist at the resolution phase

Multifocal Mass Lesions in Autoimmune Pancreatitis

A 59-year-old male patient with jaundice was referred to our hospital because of mass lesions in the pancreatic head and tail. An immunological examination revealed an elevated serum IgG4 level. Computed tomography showed two clear boundary mass lesions in the pancreatic head and tail. Magnetic resonance imaging showed that the mass lesions exhibited low intensity on T1-weighted images and iso-intensity on T2-weighted images. Magnetic resonance cholangiopancreatography showed an obstruction of the main pancreatic duct in the pancreatic head and tail. The possibility of malignant tumors could not be ruled out; therefore, we performed total pancreatectomy. A histopathological examination of the nodular lesions revealed severe lymphoplasmacytic infiltration and inflammatory change around the pancreatic ducts. Immunohistochemistry revealed diffuse infiltration of IgG4-positive plasma cells in the nodules. According to these pathological findings, we diagnosed the patient with IgG4-related multifocal mass lesions of autoimmune pancreatitis (AIP). It is difficult to distinguish between focal type AIP and pancreatic cancer. We herein report a rare case of multifocal mass lesions in AIP and include bibliographical comments

Laparoscopic Resection of an Epithelial Cyst in an Intrapancreatic Accessory Spleen

An epithelial cyst in an intrapancreatic accessory spleen (ECIAS) is rare. We herein report a case of a patient with ECIAS who underwent laparoscopic surgery. A 57-year-old woman was referred to our hospital because of a pancreatic tail tumor. She was asymptomatic, and a physical examination revealed no remarkable abnormalities. The levels of the tumor marker carbohydrate antigen 19-9 (CA19-9) and s-pancreas-1 antigen (SPan-1) were elevated. Ultrasonography showed a well-defined homogeneous cystic tumor. Computed tomography showed a well-demarcated cystic tumor in the pancreatic tail. Magnetic resonance imaging showed that the cystic tumor exhibited low intensity on T1-weighted images and high intensity on T2-weighted images. The cystic tumor was diagnosed as mucinous cystic neoplasm preoperatively. The patient underwent laparoscopic spleen-preserving distal pancreatectomy. A histopathological examination revealed the cyst wall to be lined by stratified squamous epithelium within splenic parenchyma, and the ultimate diagnosis was ECIAS. The postoperative course was uneventful, and the patient was discharged on postoperative day 12. ECIAS is very difficult to diagnose preoperatively. Laparoscopic surgery is a safe and minimally invasive procedure for patients with difficult-to-diagnose pancreatic tail tumor suspected of having low-grade malignancy