Regulation of leukocyte function-associated antigen 1-mediated adhesion by somatostatin and substance P in mouse spleen cells.
BACKGROUND
Interaction of the integrin leukocyte function-associated antigen (LFA)-1 (CD11a/CD18) with its ligands, the intercellular adhesion molecules (ICAM)-1, -2, and -3 (CD54, CD102, and CD50), is pivotal to many leukocyte adhesion events.


METHODS
To define the mechanism of the movement of leukocytes to the inflammatory site by somatostatin (SOM) and substance P (SP), we examined the expression of the adhesion molecule LFA-1 and inside-out signals for integrins, protein kinase C (PKC), Ras, Rap1, and phosphoinositide (PI) 3-kinase, in anti-CD3-, anti-CD3+SOM-, anti-CD3+SP-stimulated or unstimulated spleen cells.


RESULTS
SOM caused down-regulation of LFA-1 mRNA translation as well as of adhesion-stimulating molecules such as Rap1, Ras, and PI 3-kinase. On the other hand, SP slightly induced LFA-1 mRNA translation and activation signals for integrins. The early-phase alteration of LFA-1 mRNA translation after 3 h of culture may be due to the changes of CD8+ T cells rather than changes of CD4+ cells. In adhesion assays, SOM significantly decreased cell adhesion (p < 0.05).


CONCLUSIONS
These data suggest that SOM treatment of spleen cells, especially in CD8+ T cells, leads to downregulation of LFA-1 mRNA translation, inside-out signaling molecules for integrins (Ras, Rap1 and PI 3-kinase, but not PKC), and consequently to a decrease in the LFA-1-mediated adhesion to ICAM-1.
Kang
Bit-Na
BN
Laboratory of Veterinary Anatomy, College of Veterinary Medicine, Chungnam National University, Daegu, Korea.
Kim
Ho-Jun
HJ
Jeong
Kyu-Shik
KS
Park
Sang-Joon
SJ
Kim
Sung-Ho
SH
Kim
Se-Ra
SR
Kim
Tae-Hwan
TH
Ryu
Si-Yun
SY
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000235:genetics*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism* / Q000494:pharmacology; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D013373:Substance P; D013004:Somatostatin; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D020827:rap1 GTP-Binding Proteins; D018631:ras Proteins