Epitope-defined Monoclonal Antibodies against Multiplexin Collagens Demonstrate that Type XV and XVIII Collagens are Expressed in Specialized Basement Membranes.

Abstract

ABSTRACT. Type XV and type XVIII collagens are classified as part of multiplexin collagen superfamily and their C-terminal parts, endostatin and restin, respectively, have been shown to be anti-angiogenic in vivo and in vitro. The α1(XV) and α1(XVIII) collagen chains are reported to be localized mainly in the basement membrane zone, but their distributions in blood vessels and nonvascular tissues have yet to be thoroughly clarified. In the present study, we raised monoclonal antibodies against synthetic peptides of human α1(XV) and α1(XVIII) chains and used them for extensive investigation of the distribution of these chains. We came to the conclusion that nonvascular BMs contain mainly one of two types: subepithelial basement membranes that contained type XVIII in general, or skeletal and cardiac muscles that harbored mainly type XV. But basement membranes surrounding smooth muscle cells in vascular tissues contained one or both of them, depending on their locations. Interestingly, continuous capillaries contained both type XV and type XVIII collagens in their basement membranes; however, fenestrated or specialized capillaries such as glomeruli, liver sinusoids, lung alveoli, and splenic sinusoids expressed only type XVIII in their basement membranes, lacking type XV. This observation could imply that different functions of basement membranes in various tissues and organs use different mechanisms for the endogenous control of angiogenesis.Key words: basement membrane/type XV collagen/type XVIII collagen/capillary/smooth muscle cellThe collagen family, which consists of 20 collagen types and 38 collagen α-chains (Myllyharju and Kivirikko, 2001), are known to be major components of connective tissues and/or basement membranes (BMs). They not only serve as scaffolds for tissues and organs but also are involved in various biological events such as development, morphogenesis, inflammation, tissue repair, and filtration, as well as in various pathological processes (Olsen and Ninomiya, 1999).The BM, lying beneath epithelia and around muscle, adipose, and Schwann cells, and made visible by the periodic acid-Schiff reaction under light microscopic observation, is composed mainly of type IV collagen, laminin, nidogen, and heparan sulfate proteoglycan. Multiple components of these materials have been reported to comprise BMs in a tissue-specific fashion. For instance, six α(IV) collagen chains have been identified and at least three molecular forms distribute in various BMs‫ (ޓ‬Hudson et al., 1993;Sado et al., 1998). One form, α3/α4/α5, is specifically present in BMs where it functions as a permeability selective barrier such as in the BMs in glomerulus in kidney and alveolus in lung Saito et al., 2000). Such findings suggest the possibility that the composition of collagen IV molecules in various tissues corresponds with specific biological *To whom correspondence should be addressed: Ichiro Naito, Ph. D., Division of Ultrastructural Biology, Shigei Medical Research Institute, 2117 Yamada, Okayama 701-0202, Japan.Tel: +...

Collagen XVIII/endostatin expression in experimental endotoxemic acute renal failure

“…These data demonstrate that the endostatin detected by Western blot analysis and immunohistology is a product of collagen XVIII cleavage, which in turn indicates that, in the early phase of endotoxemic ARF, the increase in endostatin is a consequence of collagen metabolism. This is consistent with studies showing the anti-angiogenic activity of noncollagenous domain proteolytic fragments of collagen types XVIII (endostatin) and XV (restin) and type IV collagen chains a1 (arrestin), a2 (canstatin), and a3 (tumstatin) (22,30,31).…”

“…After the proteolytic process, the generated endostatin can remain associated with the basement membrane (immobilized) or be released into the circulation (soluble endostatin). It has been shown in vitro that the soluble and the immobilized forms have distinct biological activities (19)(20)(21)(22)(23)(24)(25).…”

“…In the kidney, the entire outer surface of each nephron and collecting duct is covered by a basement membrane composed primarily of laminin, collagen IV, entactin/nidogen and heparan sulfate proteoglycans, with the last category containing collagen XVIII/endostatin (21,22). The basement membrane plays an important role in the kidney since it is involved in the filtration process, as well as in cell adhesion, migration and differentiation.…”

Global Gene Expression Profiles During Acute Pathogen-Induced Pulmonary Inflammation Reveal Divergent Roles for Th1 and Th2 Responses in Tissue Repair

“…Healthy lung consists of 90% collagen types I and III, while collagen type IV, and to a lesser extent, type V, are the main components of the alveolar and capillary basement membranes (40). Recently, type XVIII collagen has also been localized to the alveolar basement membrane (41,42). Not surprisingly, then, the collagens up-regulated following egg exposure include types I, III, V, and XVIII, but not type IV.…”

Early endostatin treatment inhibits metastatic seeding of murine colorectal cancer cells in the liver and their adhesion to endothelial cells

“…Continuous capillaries contain both XV and XVIII collagen, but fenestrated capillaries (e.g. liver sinusoids, glomeruli, lung alveoli and splenic sinusoids) express only type XVIII (Tomono et al, 2002). In our hands, endostatin had no effect on subcutaneous tumours, possibly because the outgrowth of these tumours does not depend on cell seeding (data not shown; see also Schmitz et al, 2004).…”