We have previously demonstrated that Staphylococcus aureus, a highly i — Laminin

"... We here postulate that basement membrane laminin is the key antigen in driving psoriasis, inducing a T cell-mediated autoimmune response. For laminin to be considered as the key autoantigen in psoriasis, it would be reasonable to expect the following to be demonstrable: (1) that autoantigens are present in psoriatic inflammation; (2) that basement membrane laminin is perturbed in involved and uninvolved skin, and that some of the pathological changes associated with psoriasis could be predicted as a sequel to this; (3) that disruption of the basement membrane is among the earliest events in the evolution of psoriatic lesions; (4) that as streptococcal pharyngitis is the most clearly defined event to trigger or exacerbate psoriasis, then a T cell-mediated autoimmune response to laminin should be anticipated as a potential sequelae to streptococcal pharyngitis; (5) that T cells in psoriasis can be shown to react to peptides with homology to laminin; (6) that HLACw6, as the most closely related gene associated with psoriasis and which is involved in antigen expression, should be preferentially expressed within lesional psoriasis towards the basement membrane, together with other proximal associated immune activity; and (7) that there is some association between antilaminin pemphigoid, a humorally mediated autoimmune disease to skin basement membrane laminin, and psoriasis."

"Laminin-211 is a major constituent of the skeletal muscle basement membrane. It stabilizes skeletal muscle and influences signal transduction events from the myomatrix to the muscle cell. Mutations in the gene encoding the α2 chain of laminin-211 lead to congenital muscular dystrophy type 1A (MDC1A), a life-threatening disease characterized by severe hypotonia, progressive muscle weakness, and joint contractures. Common complications include severely impaired motor ability, respiratory failure, and feeding difficulties. Several adequate animal models for laminin-α2 chain deficiency exist and analyses of different MDC1A mouse models have led to a significant improvement in our understanding of MDC1A pathogenesis. Importantly, the animal models have been indispensable tools for the preclinical development of new therapeutic approaches for laminin-α2 chain deficiency, highlighting a number of important disease driving mechanisms that can be targeted by pharmacological approaches."

"Blood vessels in the central nervous system (CNS) are unique in having high electrical resistance and low permeability, which creates a selective barrier protecting sensitive neural cells within the CNS from potentially harmful components in the blood. The molecular basis of this blood–brain barrier (BBB) is found at the level of endothelial adherens and tight junction protein complexes, extracellular matrix (ECM) components of the vascular basement membrane (BM), and the influence of adjacent pericytes and astrocyte endfeet. Current evidence supports the concept that instructive cues from the BBB ECM are not only important for the development and maturation of CNS blood vessels, but they are also essential for the maintenance of vascular stability and BBB integrity. In this review, we examine the contributions of one of the most abundant ECM proteins, laminin to BBB integrity, and summarize how genetic deletions of different laminin isoforms or their integrin receptors impact BBB development, maturation, and stability."

"In adult rat testes, the basement membrane is structurally constituted by laminin and collagen chains that lay adjacent to the blood-testis barrier (BTB). It plays a crucial scaffolding role to support spermatogenesis. On the other hand, laminin-333 comprised of laminin-α3/ß3/γ3 at the apical ES (ectoplasmic specialization, a testis-specific cell-cell adherens junction at the Sertoli cell-step 8–19 spermatid interface) expressed by spermatids serves as a unique cell adhesion protein that forms an adhesion complex with α6ß1-integrin expressed by Sertoli cells to support spermiogenesis. Emerging evidence has shown that biologically active fragments are derived from basement membrane and apical ES laminin chains through proteolytic cleavage mediated by matrix metalloproteinase 9 (MMP9) and MMP2, respectively. Two of these laminin bioactive fragments: one from the basement membrane laminin-α2 chain called LG3/4/5-peptide, and one from the apical ES laminin-γ3 chain known as F5-peptide, are potent regulators that modify cell adhesion function at the Sertoli-spermatid interface (i.e., apical ES) but also at the Sertoli cell-cell interface designated basal ES at the blood-testis barrier (BTB) with contrasting effects. These findings not only highlight the physiological significance of these bioactive peptides that create a local regulatory network to support spermatogenesis, they also open a unique area of research."

"The normal microbial colonization of sites in the bodys tissues by certain bacteria requires that the bacteria first bind to extracellular secreted constituents, cell-surface membranes, or cell matrixes. This study examines two interactions of a variety of bacteria with the cell matrix noncollagenous proteins fibronectin and laminin and with basement membrane (Type IV) collagen. Adherence of bacteria to matrix proteins coated on tissue culture wells was examined with the use of radiolabeled bacteria. Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus sanguis bound well to fibronectin, laminin, and Type IV collagen, whereas a variety of gram-negative organisms did not bind. The interaction of soluble laminin, fibronectin, and Type IV collagen with bacteria was monitored by nephelometry with the use of a platelet aggregometer. S. aureus aggregated in response to fibronectin, laminin, or Type IV collagen. In contrast, gram-negative organisms did not aggregate with these proteins. It appears that fibronectin, laminin, and Type IV collagen can bind and aggregate certain gram-positive bacteria, and this binding is dependent on the surface characteristics of the organism. These adhesion molecules may play a role in the normal colonization of sites by microorganisms and in invasion during infections."

"Retinal explants from embryonic or adult mice were placed on laminin or merosin substrates and the outgrowth of optic fibers was assayed under serum-free conditions. Both substrates strongly promoted outgrowth. A blocking antibody to the β1/β3 integrin subunits completely blocked laminin-dependent growth of embryonic optic fibers but had no detectable effect on adult fibers. Similarly, a blocking antibody against the main neurite-promoting region within the globular domain of the E8 fragment of laminin inhibited growth of embryonic fibers but had no effect on adult optic fibers. The β1 integrin subunit was identified immunohistochemically on both embryonic and adult fibers. These findings indicate that adult fibers have lost the β1 function which dominates laminin-dependent growth in embryonic fibers but express a receptor for laminin-dependent growth that is not detectable in embryonic fibers. These findings suggest that there are intrinsic differences between embryonic and adult optic fibers that may have implications for regenerative failure in the central nervous system of adult mammals."