Laminin-8 (alpha4beta1gamma1) is synthesized by lymphoid cells, promotes lymphocyte migration and costimulates T cell proliferation.
Laminins are a growing family of large heterotrimeric proteins with cell adhesive and signalling functions. They are major components of basement membranes and are found in many organs, including the vasculature and other compartments of bone marrow, thymus, lymph nodes and spleen. However, expression, recognition and use of laminin isoforms by lymphoid cells are poorly understood. In the present study, lymphoid T cells (Jurkat) were found to synthesize laminin alpha4, beta1 and gamma1 mRNAs and polypeptides and to assemble the chains into laminin-8. Lymphoblastoid B (NAD-20) cells, lymphoid NK (NKL) cells and blood lymphocytes also contained laminin-8 and, after cell permeabilization, practically all blood lymphocytes reacted with mAbs to laminin beta1 and gamma1 chains. Following stimulation, blood lymphocytes secreted laminin-8, and this laminin isoform, but not laminin-10/11(alpha5beta1gamma1/alpha5beta2gamma1), promoted chemokine-induced migration of the cells. In an activation-dependent manner, purified blood CD4 T cells adhered to immobilized laminin-8 and laminin-10/11 by using alpha6beta1 integrin, but minimally to laminin-1 (alpha1beta1gamma1). Accordingly, laminin-8 and laminin-10/11, but not laminin-1, strongly costimulated proliferation of the T cells via the same integrin. Thus, lymphoid cells are able to synthesize and secrete complete laminin molecules. In addition, synthesis of laminin-8 and recognition of laminin-8 and -10/11 by lymphocytes indicate relevance of these laminin isoforms in lymphocyte physiology.
Geberhiwot
T
T
Microbiology and Tumor Biology Center and Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S 171 77 Stockholm, Sweden.
Assefa
D
D
Kortesmaa
J
J
Ingerpuu
S
S
Pedraza
C
C
Wondimu
Z
Z
Charo
J
J
Kiessling
R
R
Virtanen
I
I
Tryggvason
K
K
Patarroyo
M
M
D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D002455:Cell Division; D002465:Cell Movement; D003545:Cysteine / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology; D007797:Laminin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology*; D008715:Methionine / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013462:Sulfur Radioisotopes; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D007797:Laminin; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; C121346:laminin 1; C110308:laminin 8; D008715:Methionine; D003545:Cysteine