Increase in phagocytosis after geldanamycin treatment or heat shock: role of heat shock proteins.
The response to injury is activated at the systemic and cellular levels. At the systemic level, phagocytosis plays a key role in controlling infections and clearing necrotic and apoptotic cells. The expression of heat shock proteins (Hsp), which is a well-conserved process, is a major component of cellular response to stress. This study investigated the relationship between Hsps and phagocytosis. An increase in the phagocytosis of opsonized bacteria particles and latex beads was observed upon incubation of murine macrophages with geldanamycin (GA), a specific inhibitor of the Hsp90 family of proteins. The effect of GA on phagocytosis was blocked by coincubation with inhibitors of transcription (actinomycin D) or translation (cycloheximide), suggesting that gene expression was required. Because expression of Hsps has been observed after GA treatment, the effect of heat shock on phagocytosis was investigated. Similar to GA treatment, heat shock resulted in an actinomycin D-sensitive elevation of phagocytosis, which suggests that Hsps are involved. The increase in phagocytosis after GA treatment was not due to increased binding of opsonized particles to their respective receptors on the macrophage surface or to elevated oxidative stress. However, it was correlated with a rapid polymerization of actin in proximity to the plasma membrane. These results suggest that Hsps play a role in the modulation of the phagocytic process, which is part of the stress response.
Vega
Virginia L
VL
Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
De Maio
Antonio
A
D000199:Actins / Q000378:metabolism; D000818:Animals; D016227:Benzoquinones; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000502:physiology*; D006358:Hot Temperature; D007074:Immunoglobulin G / Q000378:metabolism; D047029:Lactams, Macrocyclic; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008863:Microspheres; D018384:Oxidative Stress / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology*
D000199:Actins; D016227:Benzoquinones; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D047029:Lactams, Macrocyclic; D011809:Quinones; C001277:geldanamycin