Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells
<p>Abstract</p> <p>Members of the carcinoembryonic antigen family (CEACAMs) are widely expressed, and, depending on the tissue, capable of regulating diverse functions including tumor promotion, tumor suppression, angiogenesis, and neutrophil activation. Four members of this family...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2008-12-01
|
| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/6/1/78 |
| _version_ | 1811294541897007104 |
|---|---|
| author | Skubitz Amy PN Skubitz Keith M |
| author_facet | Skubitz Amy PN Skubitz Keith M |
| author_sort | Skubitz Amy PN |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Members of the carcinoembryonic antigen family (CEACAMs) are widely expressed, and, depending on the tissue, capable of regulating diverse functions including tumor promotion, tumor suppression, angiogenesis, and neutrophil activation. Four members of this family, CEACAM1, CEACAM8, CEACAM6, and CEACAM3 (recognized by CD66a, CD66b, CD66c, and CD66d mAbs, respectively), are expressed on human neutrophils. CD66a, CD66b, CD66c, and CD66d antibodies each increase neutrophil adhesion to human umbilical vein endothelial cell monolayers. This increase in neutrophil adhesion caused by CD66 antibodies is blocked by CD18 mAbs and is associated with upregulation of CD11/CD18 on the neutrophil surface. To examine potential interactions of CEACAMs in neutrophil signaling, the effects on neutrophil adhesion to human umbilical vein endothelial cells of a set of CD66 mAbs was tested following desensitization to stimulation by various combinations of these mAbs. Addition of a CD66 mAb in the absence of calcium results in desensitization of neutrophils to stimulation by that CD66 mAb. The current data show that desensitization of neutrophils to any two CEACAMs results in selective desensitization to those two CEACAMs, while the cells remain responsive to the other two neutrophil CEACAMs. In addition, cells desensitized to CEACAM-3, -6, and -8 were still responsive to stimulation of CEACAM1 by CD66a mAbs. In contrast, desensitization of cells to CEACAM1 and any two of the other CEACAMs left the cells unresponsive to all CD66 mAbs. Cells desensitized to any combination of CEACAMs remained responsive to the unrelated control protein CD63. Thus, while there is significant independence of the four neutrophil CEACAMs in signaling, CEACAM1 appears to play a unique role among the neutrophil CEACAMs. A model in which CEACAMs dimerize to form signaling complexes could accommodate the observations. Similar interactions may occur in other cells expressing CEACAMs.</p> |
| first_indexed | 2024-04-13T05:18:13Z |
| format | Article |
| id | doaj.art-2688967d55b44cc1a56c213c8590763e |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-13T05:18:13Z |
| publishDate | 2008-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-2688967d55b44cc1a56c213c8590763e2022-12-22T03:00:49ZengBMCJournal of Translational Medicine1479-58762008-12-01617810.1186/1479-5876-6-78Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cellsSkubitz Amy PNSkubitz Keith M<p>Abstract</p> <p>Members of the carcinoembryonic antigen family (CEACAMs) are widely expressed, and, depending on the tissue, capable of regulating diverse functions including tumor promotion, tumor suppression, angiogenesis, and neutrophil activation. Four members of this family, CEACAM1, CEACAM8, CEACAM6, and CEACAM3 (recognized by CD66a, CD66b, CD66c, and CD66d mAbs, respectively), are expressed on human neutrophils. CD66a, CD66b, CD66c, and CD66d antibodies each increase neutrophil adhesion to human umbilical vein endothelial cell monolayers. This increase in neutrophil adhesion caused by CD66 antibodies is blocked by CD18 mAbs and is associated with upregulation of CD11/CD18 on the neutrophil surface. To examine potential interactions of CEACAMs in neutrophil signaling, the effects on neutrophil adhesion to human umbilical vein endothelial cells of a set of CD66 mAbs was tested following desensitization to stimulation by various combinations of these mAbs. Addition of a CD66 mAb in the absence of calcium results in desensitization of neutrophils to stimulation by that CD66 mAb. The current data show that desensitization of neutrophils to any two CEACAMs results in selective desensitization to those two CEACAMs, while the cells remain responsive to the other two neutrophil CEACAMs. In addition, cells desensitized to CEACAM-3, -6, and -8 were still responsive to stimulation of CEACAM1 by CD66a mAbs. In contrast, desensitization of cells to CEACAM1 and any two of the other CEACAMs left the cells unresponsive to all CD66 mAbs. Cells desensitized to any combination of CEACAMs remained responsive to the unrelated control protein CD63. Thus, while there is significant independence of the four neutrophil CEACAMs in signaling, CEACAM1 appears to play a unique role among the neutrophil CEACAMs. A model in which CEACAMs dimerize to form signaling complexes could accommodate the observations. Similar interactions may occur in other cells expressing CEACAMs.</p>http://www.translational-medicine.com/content/6/1/78 |
| spellingShingle | Skubitz Amy PN Skubitz Keith M Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells Journal of Translational Medicine |
| title | Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells |
| title_full | Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells |
| title_fullStr | Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells |
| title_full_unstemmed | Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells |
| title_short | Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells |
| title_sort | interdependency of ceacam 1 3 6 and 8 induced human neutrophil adhesion to endothelial cells |
| url | http://www.translational-medicine.com/content/6/1/78 |
| work_keys_str_mv | AT skubitzamypn interdependencyofceacam136and8inducedhumanneutrophiladhesiontoendothelialcells AT skubitzkeithm interdependencyofceacam136and8inducedhumanneutrophiladhesiontoendothelialcells |