Exogenous heat shock protein 70 binds macrophage lipid raft microdomain and stimulates phagocytosis, processing, and MHC-II presentation of antigens

Abstract

The extracellular presence of endotoxinfree heat shock protein 70 (HSP70) enhances the rate and capacity of macrophage-mediated phagocytosis at 6 times the basal rate. It is protein-specific, doseand time-dependent and involves the internalization of inert microspheres, Grampositive and -negative bacteria and fungi. Structurally, exogenous HSP70 binds the macrophage plasma membrane, specifically on its lipid raft-microdomain. Disruption of lipid rafts, HSP70-LR interaction, or denaturing HSP70 abrogates the HSPmediated increase in phagocytosis. Further, HSP70-mediated phagocytosis directly enhances the processing and presentation of internalized antigens via the endocytic MHC class-II pathway to CD4 ؉ T lymphocytes. Modulating the HSP70-LR interaction presents an opportunity to intervene at the level of hostpathogen interface: a therapeutic tool for emerging infections, especially when conventional treatment with antibiotics is ineffective (antibiotic resistance) or unavailable (rapidly spreading, endemic). These results identify a new role for HSP70, a highly conserved molecule in stimulating phagocytosis: a primordial macrophage function, thereby influencing both innate and adaptive immune responses. (Blood.

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABAA receptor and dysregulation of p130cas phosphorylation

“…Recruitment of macrophages into wound sites is a critical event for the early stage of wound healing (21,22). Increasing the recruitment of monocytes or macrophages accelerates wound healing (22,60). Inhibition of macrophage phagocytosis with antimacrophage serum also slows wound healing (31), whereas administration of heat shock protein 70, which stimulates macrophage phagocytosis (60), accelerates wound healing (29).…”

Evaluation of the E test for the assessment of synergy of antibiotic combinations against multiresistant Pseudomonas aeruginosa isolates from cystic fibrosis patients

“…As a prerequisite fluorescence from particles, which were only attached or did not interact with the phagocytes at all, had to be eliminated. This distinction was achieved by extensive washing (Algarra et al, 2002;Peiser et al, 2000), treatment with lysozyme (Hrabak et al, 2006), but most frequently by quenching of fluorescence by trypan blue (Wang et al, 2006;Wan et al, 1993;Bjerknes and Bassoe, 1984). Trypan blue absorbs light in the range from 475 -675 nm (Wang et al, 2006), which covers the wavelength of fluorescein fluorescence emission (519 nm) so that fluorescein fluorescence is efficiently quenched by trypan blue.…”

Atherogenesis and the humoral immune response to modified lipoproteins

“…The immune system also appears to recognize other by-products of macrophage activation, such as heat shock proteins (Hsp) [16]. Hsp are also immunogenic [17], and are also able to activate macrophages through interactions with Toll-like receptors [18] and lipid rafts [19,20]. Therefore, a variety of circuits are activated by modified lipoproteins and mLDL-IC, setting the conditions for a chronic inflammatory reaction in the vessel walls.…”