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Inhibition of apoptosis induced by heat shock preconditioning is associated with decreased phagocytosis in human polymorphonuclear leukocytes through inhibition of Rac and Cdc42
Author(s) -
Selva Eric,
Brest Patrick,
Loubat Agnès,
Lassalle Sandra,
Auberger Patrick,
Hofman Paul
Publication year - 2007
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/sj.icb.7100029
Subject(s) - phagocytosis , apoptosis , annexin , microbiology and biotechnology , dna fragmentation , annexin a5 , granulocyte , biology , heat shock protein , chemistry , immunology , programmed cell death , biochemistry , gene
The functionality of polymorphonuclear leukocytes (PMNL) and the exact process of the protective program employed by these cells in response to the heat shock (HS) remain ill‐defined and debated. Particularly, the mechanism of phagocytic impairment induced by the HS and the molecular events associated with the delay of apoptosis used by these cells in such condition have given conflictual data. The aim of the present work is to study the consequences of the HS in different pathways involved in human PMNL apoptosis and subsequently in human PMNL phagocytic function. We demonstrated that HS (41°C, 1 h) preconditioning induced inhibition of spontaneous PMNL apoptosis observed at 18 h in control cells incubated at 37°C. This inhibition was characterized by absence of morphological nuclear changes, decrease of DNA fragmentation, low level of annexin V expression and decrease of caspase‐3 activity. In parallel, HS increased both Hsp70 and Mcl‐1 protein levels in PMNL. Phagocytosis of latex beads by PMNL was inhibited by HS (41°C, 1 h) preconditioning despite an upregulation of CD11b, CD16 and CD47. Moreover, HS induced prolonged F actin depolymerization and inhibited both Rac and Cdc42 activation in PMNL. Finally, our results identify a new function of Mcl‐1 in HS protection against apoptosis.