STANDARD_NAME	NICK_RESPONSE_TO_PROC_TREATMENT_UP
SYSTEMATIC_NAME	M16154
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NICK_RESPONSE_TO_PROC_TREATMENT_UP
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes up-regulated in neutrophils upon treatment with activated protein C (PROC) [GeneID=5624] of pulmonary inflammation induced by bacterial lipopolysaccharide (LPS).
DESCRIPTION_FULL	Recombinant human activated protein C (rhAPC) is a natural anticoagulant with potentially important anti-inflammatory properties. In humans with severe sepsis, rhAPC treatment reduces mortality, but mechanisms responsible have not been well characterized. Accumulation of activated neutrophils in the lungs and other organs during severe infection contributes to sepsis-induced organ dysfunction, including acute inflammatory lung injury. Because neutrophils express an APC receptor, we hypothesized that immunomodulatory effects of rhAPC occur, in part, via modulation of neutrophil responses. To examine this issue, we performed a double-blinded, placebo-controlled study of rhAPC in a human model of endotoxin-induced pulmonary inflammation. Administration of rhAPC significantly reduced leukocyte accumulation to the airspaces, independent of pulmonary cytokine or chemokine release. Neutrophils recovered from bronchoalveolar lavage fluid of volunteers receiving rhAPC demonstrated decreased chemotaxis ex vivo. Decreased neutrophil chemotaxis following exposure to rhAPC was confirmed in vitro. No differences were detected in gene expression, kinase activation, cytokine release, cell survival, or apoptosis of neutrophils recovered in the presence or absence of rhAPC. These studies demonstrate that rhAPC reduces both endotoxin-induced accumulation of leukocytes in the airspaces and neutrophil chemotaxis. These rhAPC-induced effects on neutrophil function may represent a mechanism by which rhAPC improves survival in patients with sepsis.
PMID	15339848
GEOID	
AUTHORS	Nick JA,Coldren CD,Geraci MW,Poch KR,Fouty BW,O'Brien J,Gruber M,Zarini S,Murphy RC,Kuhn K,Richter D,Kast KR,Abraham E
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	202028_s_at,207021_at,216246_at,218157_x_at,218358_at,218552_at
GENE_SYMBOLS	MGC16275,ZPBP,,CDC42SE1,CRELD2,ECHDC2
FOUNDER_NAMES