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Human Mast Cells Adhere to and Migrate on Epithelial and Vascular Basement Membrane Laminins LM-332 and LM-511 via ₃β₁ Integrin¹

Wondossen Sime^*, Carolina Lunderius-Andersson, Mattias Enoksson, Patricia Rousselle, Karl Tryggvason, Gunnar Nilsson, Ilkka Harvima^¶ and Manuel Patarroyo^2,*

^* Departments of Dental Medicine and Medicine, Karolinska Institutet, Stockholm, Sweden; Institut de Biologie et Chemie de Protéines, Université Lyon I, Lyon, France; Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; and ^¶ Department of Dermatology, Kuopio University Hospital, Kuopio, Finland

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 β 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, 3-(LM-332) and 5-(LM-511) LMs, but not 1-(LM-111), 2-(LM-211), or 4-(LM-411) LMs, readily promoted adhesion and migration of cultured MCs. These activities were strongly enhanced by various stimuli. 3-LM was also able to costimulate IL-8 production. Among LM-binding integrins, MCs expressed ₃β₁, but not ₆β₁, ₇β₁, or ₆β₄, integrins. Blocking Abs to ₃β₁ integrin caused inhibition of both cell adhesion and migration on 3- and 5-LMs. Immunohistochemical studies on skin showed that MCs colocalized with epithelial and vascular basement membranes that expressed 3- and 5-LMs and that MCs expressed ₃ integrin but not ₆ integrin(s). These results demonstrate a role for 3- and 5-LMs and their ₃β₁ integrin receptor in MC biology. This may explain the intimate structural and functional interactions that MCs have with specific basement membranes.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was supported by the Swedish Cancer Society, the Swedish Research Council-Medicine, Karolinska Institutet, and Kuopio University Hospital.

² Address correspondence and reprint requests to Dr. Manuel Patarroyo, Department of Dental Medicine, Karolinska Institutet at Huddinge, SE-141 04 Stockholm, Sweden. E-mail address: Manuel.Patarroyo{at}ki.se

³ Abbreviations used in this paper: MC, mast cell; BCC, basal cell carcinoma; BM, basement membrane; CBMC, cord blood mast cell; CMC, cultured mast cell; HSA, human serum albumin; LM, laminin; INT, integrin; pFN, plasma fibronectin; rh, recombinant human; SCF, stem cell factor; SDF-1, stromal derived factor-1; TPA, 12-O-tetradecanoylphorbol-13-acetate.