Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25339677
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
DOCK2 and DOCK5 act additively in neutrophils to regulate chemotaxis, superoxide
production, and extracellular trap formation
#MMPMID25339677
Watanabe M
; Terasawa M
; Miyano K
; Yanagihara T
; Uruno T
; Sanematsu F
; Nishikimi A
; Côté JF
; Sumimoto H
; Fukui Y
J Immunol
2014[Dec]; 193
(11
): 5660-7
PMID25339677
show ga
Neutrophils are highly motile leukocytes that play important roles in the innate
immune response to invading pathogens. Neutrophils rapidly migrate to the site of
infections and kill pathogens by producing reactive oxygen species (ROS).
Neutrophil chemotaxis and ROS production require activation of Rac small GTPase.
DOCK2, an atypical guanine nucleotide exchange factor (GEF), is one of the major
regulators of Rac in neutrophils. However, because DOCK2 deficiency does not
completely abolish fMLF-induced Rac activation, other Rac GEFs may also
participate in this process. In this study, we show that DOCK5 acts with DOCK2 in
neutrophils to regulate multiple cellular functions. We found that fMLF- and
PMA-induced Rac activation were almost completely lost in mouse neutrophils
lacking both DOCK2 and DOCK5. Although ?2 integrin-mediated adhesion occurred
normally even in the absence of DOCK2 and DOCK5, mouse neutrophils lacking DOCK2
and DOCK5 exhibited a severe defect in chemotaxis and ROS production. Similar
results were obtained when human neutrophils were treated with CPYPP, a
small-molecule inhibitor of these DOCK GEFs. Additionally, we found that DOCK2
and DOCK5 regulate formation of neutrophil extracellular traps (NETs). Because
NETs are involved in vascular inflammation and autoimmune responses, DOCK2 and
DOCK5 would be a therapeutic target for controlling NET-mediated inflammatory
disorders.
free
free
free
