Human mast cells adhere to and migrate on epithelial and vascular basement membrane laminins LM-332 and LM-511 via alpha3beta1 integrin.
Mast cells (MCs) are multifunctional effectors of the immune system that are distributed in many tissues, often in close association with the basement membrane of blood vessels, epithelium and nerves. Laminins (LMs), a family of large alphabetagamma heterotrimeric proteins, are major components of basement membrane that strongly promote cell adhesion and migration. In this study, we investigated the role of LM isoforms and their integrin receptors in human MC biology in vitro. In functional assays, alpha3-(LM-332) and alpha5-(LM-511) LMs, but not alpha1-(LM-111), alpha2-(LM-211), or alpha4-(LM-411) LMs, readily promoted adhesion and migration of cultured MCs. These activities were strongly enhanced by various stimuli. alpha3-LM was also able to costimulate IL-8 production. Among LM-binding integrins, MCs expressed alpha(3)beta(1), but not alpha(6)beta(1), alpha(7)beta(1), or alpha(6)beta(4), integrins. Blocking Abs to alpha(3)beta(1) integrin caused inhibition of both cell adhesion and migration on alpha3- and alpha5-LMs. Immunohistochemical studies on skin showed that MCs colocalized with epithelial and vascular basement membranes that expressed alpha3- and alpha5-LMs and that MCs expressed alpha(3) integrin but not alpha(6) integrin(s). These results demonstrate a role for alpha3- and alpha5-LMs and their alpha(3)beta(1) integrin receptor in MC biology. This may explain the intimate structural and functional interactions that MCs have with specific basement membranes.
Sime
Wondossen
W
Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
Lunderius-Andersson
Carolina
C
Enoksson
Mattias
M
Rousselle
Patricia
P
Tryggvason
Karl
K
Nilsson
Gunnar
G
Harvima
Ilkka
I
Patarroyo
Manuel
M
D000368:Aged; D000369:Aged, 80 and over; D001485:Basement Membrane / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D039201:Integrin alpha3beta1 / Q000097:blood / Q000502:physiology*; D007797:Laminin / Q000097:blood / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D020033:Protein Isoforms / Q000097:blood / Q000502:physiology
D039201:Integrin alpha3beta1; D007797:Laminin; D020033:Protein Isoforms; C097043:laminin alpha5; C095567:laminin alpha 3