Mechanochemical Regulation of Cell Adhesion by Incorporation of Synthetic Polymers to Plasma Membranes.

Chemical control of cell-cell interactions using synthetic materials is useful for a wide range of biomedical applications. Herein, we report a method to regulate cell adhesion and dispersion by introducing repulsive forces to live cell membranes. To induce repulsion, we tethered amphiphilic polymers, such as cholesterol-modified poly(ethylene glycol) (PEG-CLS), to cell membranes.

Roles of the ribosomal protein S19 dimer and chemically induced apoptotic cells as a tumor vaccine in syngeneic mouse transplantation models.

We examined the roles of a chemotherapeutic reagent in both inducing apoptosis and conferring acquired tumor immunity using mouse syngeneic tumor transplantation models. A chemotherapeutic reagent, cis-diamminedichloroplatinum (II), effectively induced apoptosis in Colon-26 cells originating from a BALB/c mouse. Three intradermal inoculations of cis-diamminedichloroplatinum (II)-treated Colon-26 cells conferred tumor immunity against viable Colon-26 cells in BALB/c mice but not in athymic BALB/c mice.

Role of ribosomal protein S19-like plasma protein in blood coagulum resorption.

Western blot analyses and monocyte chemoattraction analyses of guinea pig plasma and serum indicated the presence of a plasma protein indistinguishable from ribosomal protein S19 and the cross-linked dimerization of it gaining monocyte chemotactic capacity in association with blood coagulation as in the case of human. When coagula preformed in vitro were intraperitoneally inserted into guinea pigs, they were rapidly covered by macrophages within 24h concomitant with an intra-coagulum macrophage infiltration. Differences were observed between the surface macrophages and the penetrating macrophages in ultrastructural, histochemical and immunohistochemical analyses.

Base of molecular mimicry between human ribosomal protein S19 dimer and human C5a anaphylatoxin.

The crosslinked homodimer of human ribosomal protein S19 (hRP S19) but not hRP S19 monomer shares the hC5a receptor ligation capacity with anaphylatoxin hC5a. The hRP S19 dimer engages hC5a receptor-bearing monocytes in chemotactic movement and secretion as does hC5a. Two submolecular regions essential for the receptor ligation were already identified in hRP S19 as well as in hC5a.

A plasma protein indistinguishable from ribosomal protein S19: conversion to a monocyte chemotactic factor by a factor XIIIa-catalyzed reaction on activated platelet membrane phosphatidylserine in association with blood coagulation.

A monocyte-chemoattracting factor is generated during blood coagulation and during clotting of platelet-rich plasma. This chemotactic factor attracts monocytes as a ligand of the C5a receptor; however, it inhibits C5a-induced neutrophil chemotaxis as an apparent receptor antagonist. The curious dual function of the serum monocyte chemotactic factor resembles that of the cross-linked homodimer of ribosomal protein S19 (RP S19).

Pro- and anti-apoptotic dual functions of the C5a receptor: involvement of regulator of G protein signaling 3 and extracellular signal-regulated kinase.

When apoptosis is initiated by manganese (II) loading, hyperthermia or thapsigargin treatment, human HL-60 and AsPC-1 cells initiate de novo synthesis of the C5a receptor (C5aR) and generation of its ligand, the ribosomal protein S19 (RP S19) homodimer. The ligand-receptor interaction, in an autocrine/paracrine fashion, promotes apoptosis, which can be bypassed by exogenous administration of C5a, another ligand. The proapoptotic function of the RP S19 dimer is reproduced by a C5a/RPS19 chimera that contains the body of C5a and the C-terminal region (Ile134-His145) of RP S19.

Agonistic and antagonistic effects of C5a-chimera bearing S19 ribosomal protein tail portion on the C5a receptor of monocytes and neutrophils, respectively.

C-terminus of S19 ribosomal protein (RP S19) endows the cross-linked homodimer with a dual effect on the C5a receptor in leucocyte chemoattraction; agonistic effect on the monocyte receptor, and antagonistic effect on the neutrophil receptor. C5a exhibits the uniform agonistic effect on this receptor of both cell types. We have currently prepared a recombinant C5a-chimeric protein bearing the C-terminus of RP S19 (C5a/RP S19 chimera) to be used as a substitute of the RP S19 dimer.