Phagocytosis by macrophages mediated by receptors for denatured proteins - dependence on tyrosine protein kinases

Abstract

Previous studies have demonstrated that some components of the leukocyte cell membrane, CR3 (Mac-1, CD11b/CD18) and p150/95, are able to bind to denatured proteins. Thus, it is of interest to know which effector functions of these cells can be triggered by these receptors when they interact with particles or surfaces covered with denatured proteins. In the present study we analyzed their possible role as mediators of phagocytosis of red cells covered with denatured bovine serum albumin (BSA) by mouse peritoneal macrophages. We observed that a) macrophages are able to recognize (bind to) these red cells, b) this interaction can be inhibited by denatured BSA in the fluid phase, c) there is no phagocytosis of these particles by normal macrophages, d) phagocytosis mediated by denatured BSA can be, however, effectively triggered in inflammatory macrophages induced by glycogen or in macrophages activated in vivo with LPS, and e) this phagocytic capacity is strongly dependent on the activity of tyrosine protein kinases in its signal transduction pathway, as demonstrated by using three kinds of enzyme inhibitors (genistein, quercetin and herbimycin A).

Classically and alternatively activated bone marrow derived macrophages differ in cytoskeletal functions and migration towards specific CNS cell types

“…However, flavonoids do more than scavenge. Quercetin could also mediate its effects due to the inhibition of protein tyrosine kinases, which are involved in the signaling of the engulfment phase of CR3 mediated phagocytosis [72]. Luteolin has effects on the actin cytoskeleton [73,74] through Rho and Rac [75] and could thereby affect phagocytosis.…”

Acute phase proteins are major clients for the chaperone action of α2-macroglobulin in human plasma

“…the force exerted on soluble proteins and the extracellular domains of plasma membrane proteins as blood plasma is pumped throughout the body), which can induce protein misfolding (Bekard et al 2011;Di Stasio and De Cristofaro 2010). Thus, the discovery and characterization of molecules that specifically recognise extracellular misfolded proteins, be they secreted chaperones (French et al 2008;Humphreys et al 1999;Yerbury et al 2005), cell surface receptors (Jana et al 2008;Husemann et al 2002;Herczenik et al 2007;Udan et al 2008;Hespanhol and Mantovani 2002;Davis 1992) or elements of protease systems (Kranenburg et al 2002), will shed important light on how proteostasis is maintained extracellularly and may help to uncover the causes of serious diseases.…”

The Biocompatibility of Implant Materials

“…Such trigger molecules include mannose sugar moieties, complement molecules, the Fc portion of antibodies, and denatured proteins (Hespanhol and Mantovani, 2002). For 100 years or more, it has been clear that living cells interact with and attach to different materials in different ways.…”