The leukocyte function-associated antigen-1 (LFA-1) is involved in the interferon-alpha response induced by herpes simplex virus in blood leukocytes.
The role of the leukocyte function-associated antigen-1 (LFA-1) family of integrins (beta 2 integrins) in the interferon-alpha (IFN-alpha) response was examined, using human peripheral blood mononuclear cells (PBMCs) stimulated in vitro by glutaraldehyde-fixed Herpes simplex virus-infected WISH amnion cells. Monoclonal antibodies (mAbs) to the beta 2 chain (CD18) and to the alpha chain of LFA-1 (CD11a) reduced the number of IFN-alpha-producing cells (IPCs) by 30-50%, but mAbs to CD11b or c caused no inhibition. The IB4 mAb to CD18 was inhibitory when added during the first 2 h of the IFN-alpha response, but did not alter its kinetic. In contrast, the IB4 prevented the early enhancement of the IFN-alpha response caused by addition of interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF). However, a delayed down-regulation of the IPC response occurred in such PBMC cultures, and a paradoxical increase in the total production of IFN-alpha. The results suggest that LFA-1 (CD11a/CD18) participates in the early phase of the IFN-alpha response and may be activated by cytokines such as IL-3 and GM-CSF.
Cederblad
B
B
Department of Veterinary Microbiology, Swedish University of Agricultural Sciences, Uppsala.
Sandberg
K
K
Alm
G V
GV
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D018821:CD18 Antigens; D002460:Cell Line; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1; D018139:Simplexvirus / Q000276:immunology*; D017186:Titrimetry
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016898:Interferon-alpha; D016169:Lymphocyte Function-Associated Antigen-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor