CEACAM1 (CD66a) mediates delay of spontaneous and Fas ligand-induced apoptosis in granulocytes.
Granulocytes form the first and fastest line of defense against pathogenic infections. Their survival is limited by apoptosis, a process that is critical for the resolution of inflammation. Pro-apoptotic and pro-inflammatory cytokines, as well as several receptors, can alter the lifespan of granulocytes. Here we report that the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is involved in the regulation of granulocyte survival. Until now CEACAM1 is described to control cell proliferation, cell migration, tumor growth, angiogenesis and diverse leukocyte functions. However, very little is known about its role in granulocytes. We found that CEACAM1 expression in resting rat granulocytes is significantly higher than in other leukocyte subtypes. Stimulation led to a strongly increased CEACAM1 cell surface expression and to release of soluble CEACAM1. DNA fragmentation assays and annexin V staining revealed that binding of CEACAM1-specific antibodies, Fab fragments and soluble CEACAM1-Fc constructs to cell surface-expressed CEACAM1 causes a delay of spontaneous and Fas ligand (CD95L)-induced apoptosis. Tyrosine phosphorylation of CEACAM1-L, its association with SHP-1, the activation of Erk1/2 and caspase-3 appeared to be crucial for the CEACAM1-mediated anti-apoptotic effect. These findings provide evidence that CEACAM1 influences the resolution of inflammation by prolonging the survival of rat granulocytes.
Singer
Bernhard B
BB
Institut für Biochemie und Molekularbiologie, Campus Benjamin Franklin, Charité, Berlin, Germany. BBSinger@gmx.de
Klaile
Esther
E
Scheffrahn
Inka
I
Müller
Mario M
MM
Kammerer
Robert
R
Reutter
Werner
W
Obrink
Björn
B
Lucka
Lothar
L
D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000502:physiology; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D053222:Fas Ligand Protein; D006098:Granulocytes / Q000166:cytology / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D051381:Rats; D011915:Rats, Inbred BUF; D017208:Rats, Wistar; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D017304:Annexin A5; D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D014443:Tyrosine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D048049:Extracellular Signal-Regulated MAP Kinases; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509250:Ptpn6 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases